Is STAG2 p.Pro1077= (c.3231A>G) pathogenic?

STAG2 p.Pro1077= (c.3231A>G) is classified Likely benign in STAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). Very rare (popmax 0.00874%, afr).

How common is STAG2 p.Pro1077= (c.3231A>G) in the general population?

STAG2 p.Pro1077= (c.3231A>G) is very rare (popmax 0.00874%, afr) (gnomAD).

STAG2 p.Pro1077=

c.3231A>G · VCV3629361

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00874%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -4.8, phastCons 1
Overall
CADD	8.074	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00874% African / African-American · 5/57,209 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.000414% 5/1,208,191 alleles · very rare exomes 3/1,096,189 · genomes 2/112,002 · 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.Pro1077=
Coding: c.3231A>G
MANE Select: NM_001042750
Type: single nucleotide variant
Location: chrX:124086724 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 1077: 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); the 'disordered' region

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-pro1077 (accessed [today's date]).

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