NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jan 19, 2026
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000443069.34

Allele description [Variation Report for NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser)]

NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser)

Gene:

SERPINA1:serpin family A member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.13

Genomic location:

Preferred name:

NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser)

HGVS:

NC_000014.9:g.94378529G>A
NG_008290.1:g.17164C>T
NM_000295.5:c.1177C>TMANE SELECT
NM_001002235.3:c.1177C>T
NM_001002236.3:c.1177C>T
NM_001127700.2:c.1177C>T
NM_001127701.2:c.1177C>T
NM_001127702.2:c.1177C>T
NM_001127703.2:c.1177C>T
NM_001127704.2:c.1177C>T
NM_001127705.2:c.1177C>T
NM_001127706.2:c.1177C>T
NM_001127707.2:c.1177C>T
NP_000286.3:p.Pro393Ser
NP_001002235.1:p.Pro393Ser
NP_001002236.1:p.Pro393Ser
NP_001121172.1:p.Pro393Ser
NP_001121173.1:p.Pro393Ser
NP_001121173.1:p.Pro393Ser
NP_001121174.1:p.Pro393Ser
NP_001121175.1:p.Pro393Ser
NP_001121176.1:p.Pro393Ser
NP_001121177.1:p.Pro393Ser
NP_001121178.1:p.Pro393Ser
NP_001121179.1:p.Pro393Ser
LRG_575t1:c.1177C>T
LRG_575:g.17164C>T
LRG_575p1:p.Pro393Ser
NC_000014.8:g.94844866G>A
NM_000295.4:c.1177C>T
NM_001127701.1:c.1177C>T

Protein change:

P393S

Links:

dbSNP: rs61761869

Molecular consequence:

NM_000295.5:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001002235.3:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001002236.3:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127700.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127701.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127702.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127703.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127704.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127705.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127706.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127707.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000343429	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 9, 2017)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11474657, 18515255, 19437508, 19654085, 22723858, 10234508, 27296815 Citation Link,
SCV000516540	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 9, 2025)	germline	clinical testing	Citation Link,
SCV004130295	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (May 1, 2024)	germline	clinical testing	Citation Link,
SCV005414249	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 13, 2024)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 10234508, 10878477, 11474657, 18024524, 18515255, 19437508, 21474916, 22723858, 27296815, 29882371, 31661293, 31980526, 37277845, 37622442, 25741868
SCV007599270	Dasa	criteria provided, single submitter (DASA Assertion Criteria)	Pathogenic (Jan 19, 2026)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10234508, 27296815 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	5	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Biochemical and molecular diagnosis of alpha 1 antitrypsin deficiency in a Tunisian family].

Denden S, Braham W, Amri F, Lakhdar R, Lefranc G, Knani J, Ben Chibani J, Haj Khelil A.

Ann Biol Clin (Paris). 2009 Jul-Aug;67(4):441-5. doi: 10.1684/abc.2009.0340. French.

PubMed [citation]

PMID:: 19654085

Characterization of the new alpha-1-antitrypsin-deficient PI M-type allele, PI M(vall d'hebron) (Pro(369)-->Ser).

Jardi R, Rodriguez-Frias F, Lopez-Talavera JC, Miravitlles M, Cotrina M, Costa X, Pascual C, Vidal R.

Hum Hered. 2000 Sep-Oct;50(5):320-1. No abstract available.

PubMed [citation]

PMID:: 10878477

See all PubMed Citations (16)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000343429.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (7)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		4	not provided	not provided	not provided

From GeneDx, SCV000516540.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as P369S or Mwurzburg allele using alternate nomenclature; This variant is associated with the following publications: (PMID: 31980526, 10234508, 27296815, 11474657, 31447099, 34426522, 34308104, 31661293, 21228398, 29882371, 38791420, 37688579, 22723858)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004130295.22

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

SERPINA1: PM3:Strong, PM1, PM2, PM5, PP4:Moderate, PS3:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV005414249.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (15)

Description

PP3, PP4, PM2_moderate, PM5, PS3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Dasa, SCV007599270.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser) is a missense variant that results in the substitution of proline with serine. Functional evidence supports a deleterious effect on the gene or gene product (PMID: 10234508; PMID: 27296815). This variant has been recurrently observed in individuals with related phenotype (PMID: 10234508; PMID: 27296815). Multiple computational predictions support a deleterious effect on the gene or gene product. The variant is present at low frequency in population datasets. Based on the available data, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 20, 2026

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