Is BEND5 p.Met86Val (c.256A>G) pathogenic?

BEND5 p.Met86Val (c.256A>G) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.1733); Ultra-rare (popmax 0.026%, afr).

How common is BEND5 p.Met86Val (c.256A>G) in the general population?

BEND5 p.Met86Val (c.256A>G) is ultra-rare (popmax 0.026%, afr) (gnomAD).

What do computational predictors say about BEND5 p.Met86Val (c.256A>G)?

AlphaMissense predicts likely benign (score 0.1733) — an in-silico prediction, not a clinical call.

BEND5 p.Met86Val

c.256A>G · VCV3480436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.026%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1733	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -4.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.01 · regional, not allelic
Overall
CADD	20.1	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 0.026% African / African-American · 19/73,062 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0141%

Overall 0.00135% 21/1,551,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.026%	3,845
Remaining individualsnot grpmax-eligible	0.00333%	30,047

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.Met86Val
Coding: c.256A>G
MANE Select: NM_032785 · reported on NM_024603
Type: single nucleotide variant
Location: chr1:48761441 (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-met86val (accessed [today's date]).

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