Is STAG2 p.Val413Phe (c.1237G>T) pathogenic?

STAG2 p.Val413Phe (c.1237G>T) is classified Uncertain significance in STAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely pathogenic (0.9945); Absent from gnomAD v4.1.

How common is STAG2 p.Val413Phe (c.1237G>T) in the general population?

STAG2 p.Val413Phe (c.1237G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAG2 p.Val413Phe (c.1237G>T)?

AlphaMissense predicts likely pathogenic (score 0.9945) — an in-silico prediction, not a clinical call.

STAG2 p.Val413Phe

c.1237G>T · rs2521586906 · VCV2502714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9945	likely pathogenic
REVEL	0.72	pathogenic-leaning
SaProt	LLR -13.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 49 kb · p 1.5e-34 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STAG2
Protein: p.Val413Phe
Coding: c.1237G>T
MANE Select: NM_001042750
dbSNP: rs2521586906
Type: single nucleotide variant
Location: chrX:124056168 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 413: 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); an α-helix

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

Similar variants

STAG2 p.Val413= Benign ★ same residue
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

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-val413phe (accessed [today's date]).

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