Is STAG2 p.Ile720= (c.2160C>A) pathogenic?

STAG2 p.Ile720= (c.2160C>A) is classified Likely benign in STAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Very rare (popmax 0.00379%, afr).

How common is STAG2 p.Ile720= (c.2160C>A) in the general population?

STAG2 p.Ile720= (c.2160C>A) is very rare (popmax 0.00379%, afr) (gnomAD).

STAG2 p.Ile720=

c.2160C>A · rs756185760 · VCV1920748

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00379%, afr)

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 -0.54, phastCons 1
Overall
CADD	6.812	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00379% African / African-American · 2/52,701 alleles

Filtering AF 0.000629% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000236%

Overall 0.000254% 3/1,182,281 alleles · very rare exomes 3/1,082,728 · genomes 0/99,553 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00379%	26,351
Admixed American	0.00234%	42,754

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.Ile720=
Coding: c.2160C>A
MANE Select: NM_001042750
dbSNP: rs756185760
Type: single nucleotide variant
Location: chrX:124066238 (GRCh38)
Structure: AlphaFold pLDDT 80.07 · 10 PDB
Residue 720: 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.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-ile720 (accessed [today's date]).

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