Is STAG2 p.Pro817Ser (c.2449C>T) pathogenic?

STAG2 p.Pro817Ser (c.2449C>T) is classified Uncertain significance in STAG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-09). AlphaMissense: likely pathogenic (0.9154); Very rare (popmax 0.0022%, amr).

How common is STAG2 p.Pro817Ser (c.2449C>T) in the general population?

STAG2 p.Pro817Ser (c.2449C>T) is very rare (popmax 0.0022%, amr) (gnomAD).

What do computational predictors say about STAG2 p.Pro817Ser (c.2449C>T)?

AlphaMissense predicts likely pathogenic (score 0.9154) — an in-silico prediction, not a clinical call.

STAG2 p.Pro817Ser

c.2449C>T · VCV3696395

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9154 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9154	likely pathogenic
REVEL	0.211	benign-leaning
SaProt	LLR -11.45	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 49 kb · p 1.5e-34 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% Admixed American · 1/45,371 alleles

Overall 8.3e-05% 1/1,204,971 alleles · very rare exomes 1/1,092,944 · genomes 0/112,027 · joint denominator

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.Pro817Ser
Coding: c.2449C>T
MANE Select: NM_001042750
Type: single nucleotide variant
Location: chrX:124071239 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 817: an α-helix; 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.Pro817Ala Uncertain significance ★ ⚠ 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-pro817ser (accessed [today's date]).

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