Is STAG3 p.Pro431= (c.1293A>C) pathogenic?

STAG3 p.Pro431= (c.1293A>C) is classified Benign in STAG3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-15). Common (popmax 67%, eas) — too common for a highly-penetrant pathogenic allele; Associated with spermatogenic failure 61.

What condition is associated with STAG3 p.Pro431= (c.1293A>C)?

STAG3 p.Pro431= (c.1293A>C) is associated with spermatogenic failure 61, premature ovarian failure 8 (ClinVar).

STAG3 p.Pro431=

Q: How common is STAG3 p.Pro431= (c.1293A>C) in the general population?

STAG3 p.Pro431= (c.1293A>C) is common (popmax 67%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1293A>C · rs3735241 · VCV1243986

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 67%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

spermatogenic failure 61

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -4.6
Overall
CADD	0.623	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 67% East Asian · 30,060/44,872 alleles

Filtering AF 66.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.1%

Overall 49.2% 794,454/1,613,828 alleles · common exomes 721,519/1,461,796 · genomes 72,935/152,032 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	67%	1
Admixed American	64.1%	2
Amishnot grpmax-eligible	57.9%	2
Ashkenazi Jewishnot grpmax-eligible	53.6%	2
Finnishnot grpmax-eligible	50.5%	2
Middle Eastern	50.5%	2
Remaining individualsnot grpmax-eligible	49.3%	2
European (non-Finnish)	48.8%	2
South Asian	42%	2
African / African-American	38.7%	3

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: STAG3
Protein: p.Pro431=
Coding: c.1293A>C
MANE Select: NM_001282717
dbSNP: rs3735241
Type: single nucleotide variant
Location: chr7:100198523 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.46

Full STAG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 61 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: premature ovarian failure 8

Similar variants

STAG3 p.Arg926Ter Pathogenic/Likely pathogenic ★★ same condition
STAG3 c.1245-26T>C Benign ★★ same condition
STAG3 c.1573+41C>G Benign ★★ same condition
STAG3 p.Ile815= Benign ★★ same condition
STAG3 p.Leu16Phe Benign ★★ same condition
STAG3 p.Thr36Pro Benign ★★ same condition
STAG3 p.Arg1018Ter Pathogenic ★ same condition
STAG3 p.Arg438Ter Likely pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/stag3-p-pro431 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown