Is BEND2 p.Val261Gly (c.782T>G) pathogenic?

BEND2 p.Val261Gly (c.782T>G) is classified Benign in BEND2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-03-29). AlphaMissense: likely benign (0.0671); Common (popmax 7.78%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BEND2 p.Val261Gly (c.782T>G)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

BEND2 p.Val261Gly

Q: How common is BEND2 p.Val261Gly (c.782T>G) in the general population?

BEND2 p.Val261Gly (c.782T>G) is common (popmax 7.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.782T>G · rs74391498 · VCV783906

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.78%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.096	GERP -3.3
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.98 · regional, not allelic
Overall
CADD	0.694	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 7.78% African / African-American · 4,447/57,181 alleles

Filtering AF 7.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.51%

Overall 0.443% 5,354/1,209,651 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.78%	13
Remaining individualsnot grpmax-eligible	0.721%	139
Admixed American	0.63%	159
Middle Eastern	0.551%	181
Finnishnot grpmax-eligible	0.0579%	1,727
South Asian	0.0299%	3,341
European (non-Finnish)	0.0231%	4,323
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,033

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: BEND2
Protein: p.Val261Gly
Coding: c.782T>G
MANE Select: NM_153346
dbSNP: rs74391498
Type: single nucleotide variant
Location: chrX:18203626 (GRCh38)
Structure: AlphaFold pLDDT 49.94

Full BEND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND2 p.Gln198His Benign ★★ same type
BEND2 p.Gly580Val Benign ★★ same type
BEND2 p.Ser183Ile Benign ★★ same type
BEND2 p.Thr367= Likely benign ★★ same type
BEND2 p.Ala185Gly Uncertain significance ★ ⚠ same type
BEND2 p.Ala193Thr Uncertain significance ★ ⚠ same type
BEND2 p.Ala222Ser Uncertain significance ★ ⚠ same type
BEND2 p.Ala270Ser 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/bend2-p-val261gly (accessed [today's date]).

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