Is STAG2 p.Asp338= (c.1014T>C) pathogenic?

STAG2 p.Asp338= (c.1014T>C) is classified Benign/Likely benign in STAG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-18). Very rare (popmax 0.00885%, amr).

How common is STAG2 p.Asp338= (c.1014T>C) in the general population?

STAG2 p.Asp338= (c.1014T>C) is very rare (popmax 0.00885%, amr) (gnomAD).

STAG2 p.Asp338=

c.1014T>C · rs755412065 · VCV1624352

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00885%, amr)

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 1.9	GERP -0.44, phastCons 1
Overall
CADD	10.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00885% Admixed American · 4/45,202 alleles

Filtering AF 0.00296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00179%

Overall 0.00282% 34/1,203,808 alleles · very rare exomes 32/1,092,018 · genomes 2/111,790 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00885%	11,300
Remaining individualsnot grpmax-eligible	0.00845%	11,840
East Asian	0.00298%	33,513
European (non-Finnish)	0.0028%	35,687

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: STAG2
Protein: p.Asp338=
Coding: c.1014T>C
MANE Select: NM_001042750
dbSNP: rs755412065
Type: single nucleotide variant
Location: chrX:124050306 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 338: the scd domain; a UniProt-annotated variant site (in hpe13 and mkms; patient cells show decreased protein abundance; increased sister chromatid cohesion); a UniProt-annotated variant site (in mkms); a UniProt-annotated variant site (in hpe13)

Full STAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STAG2 p.Arg1012Ter Pathogenic ★★ same type
STAG2 p.Arg1033Ter Pathogenic ★★ same type
STAG2 c.1018-3T>A Uncertain significance ★★ same type
STAG2 c.2924+3A>G Uncertain significance ★★ same type
STAG2 c.2924+5T>A Uncertain significance ★★ same type
STAG2 c.3784-3T>C Uncertain significance ★★ same type
STAG2 p.Ala428Gly Uncertain significance ★★ ⚠ same type
STAG2 p.Ala532Val Uncertain significance ★★ ⚠ same type

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/stag2-p-asp338 (accessed [today's date]).

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