Is BEND5 p.Val161Met (c.481G>A) pathogenic?

BEND5 p.Val161Met (c.481G>A) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.00666%, amr).

How common is BEND5 p.Val161Met (c.481G>A) in the general population?

BEND5 p.Val161Met (c.481G>A) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about BEND5 p.Val161Met (c.481G>A)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

BEND5 p.Val161Met

c.481G>A · rs374150750 · VCV3133709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 0.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.01 · regional, not allelic
Overall
CADD	17.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% Admixed American · 4/60,026 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00124% 20/1,614,196 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,006
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0048%	20,835
East Asian	0.00446%	22,441
European (non-Finnish)	0.000508%	196,671

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: BEND5
Protein: p.Val161Met
Coding: c.481G>A
MANE Select: NM_032785 · reported on NM_024603
dbSNP: rs374150750
Type: single nucleotide variant
Location: chr1:48759164 (GRCh38)

Full BEND5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/bend5-p-val161met (accessed [today's date]).

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