Is STAG2 p.Asp757= (c.2271C>T) pathogenic?

STAG2 p.Asp757= (c.2271C>T) is classified Likely benign in STAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). Very rare (popmax 0.00034%, nfe).

How common is STAG2 p.Asp757= (c.2271C>T) in the general population?

STAG2 p.Asp757= (c.2271C>T) is very rare (popmax 0.00034%, nfe) (gnomAD).

STAG2 p.Asp757=

c.2271C>T · rs769331923 · VCV1648163

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

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 -0.11	GERP -4, phastCons 0.53
Overall
CADD	6.749	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 3/883,186 alleles

Filtering AF 9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000339% 4/1,179,846 alleles · very rare exomes 3/1,068,041 · genomes 1/111,805 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00216%	46,237
European (non-Finnish)grpmax	0.00034%	294,396

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp757=
Coding: c.2271C>T
MANE Select: NM_001042750
dbSNP: rs769331923
Type: single nucleotide variant
Location: chrX:124068569 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 757: 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.Asp757Tyr 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-asp757 (accessed [today's date]).

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