Is BEND5 p.Val381Gly (c.1142T>G) pathogenic?

BEND5 p.Val381Gly (c.1142T>G) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: ambiguous (0.3495); Very rare (popmax 0.00668%, afr).

How common is BEND5 p.Val381Gly (c.1142T>G) in the general population?

BEND5 p.Val381Gly (c.1142T>G) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about BEND5 p.Val381Gly (c.1142T>G)?

AlphaMissense predicts ambiguous (score 0.3495) — an in-silico prediction, not a clinical call.

BEND5 p.Val381Gly

c.1142T>G · VCV4645761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3495 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3495	ambiguous
REVEL	0.219	benign-leaning
SaProt	LLR -6.18	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 15 kb · p 1.6e-09 · regional, not allelic
Overall
CADD	24.6	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 0.00668% African / African-American · 5/74,906 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000434% 7/1,612,120 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,981
South Asian	0.0022%	45,403

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.Val381Gly
Coding: c.1142T>G
MANE Select: NM_032785 · reported on NM_024603
Type: single nucleotide variant
Location: chr1:48728010 (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-val381gly (accessed [today's date]).

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