Is BEND5 p.Ile119Met (c.357C>G) pathogenic?

BEND5 p.Ile119Met (c.357C>G) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.0731); Ultra-rare (popmax 0.023%, nfe).

How common is BEND5 p.Ile119Met (c.357C>G) in the general population?

BEND5 p.Ile119Met (c.357C>G) is ultra-rare (popmax 0.023%, nfe) (gnomAD).

What do computational predictors say about BEND5 p.Ile119Met (c.357C>G)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

BEND5 p.Ile119Met

c.357C>G · rs777996088 · VCV2205050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.01 · regional, not allelic
Overall
CADD	21.2	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 0.023% European (non-Finnish) · 264/1,145,680 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0199%

Overall 0.0183% 283/1,548,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0266%	3,755
European (non-Finnish)grpmax	0.023%	4,340
African / African-American	0.00275%	36,400
South Asian	0.0012%	83,152

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile119Met
Coding: c.357C>G
MANE Select: NM_032785 · reported on NM_024603
dbSNP: rs777996088
Type: single nucleotide variant
Location: chr1:48761340 (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-ile119met (accessed [today's date]).

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