Is BEND4 p.Ala97Pro (c.289G>C) pathogenic?

BEND4 p.Ala97Pro (c.289G>C) is classified Uncertain significance in BEND4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely benign (0.1319); Very rare (popmax 0.00779%, afr).

How common is BEND4 p.Ala97Pro (c.289G>C) in the general population?

BEND4 p.Ala97Pro (c.289G>C) is very rare (popmax 0.00779%, afr) (gnomAD).

What do computational predictors say about BEND4 p.Ala97Pro (c.289G>C)?

AlphaMissense predicts likely benign (score 0.1319) — an in-silico prediction, not a clinical call.

BEND4 p.Ala97Pro

c.289G>C · rs866025967 · VCV2474784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1319 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00779%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1319	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.05	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 1.4	GERP -0.19, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 35 kb · p 0.85 · regional, not allelic
Overall
CADD	20.9	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 0.00779% African / African-American · 5/64,214 alleles

Filtering AF 0.00297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000457% 6/1,313,124 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00779%	12,843
Remaining individualsnot grpmax-eligible	0.00203%	49,228

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: BEND4
Protein: p.Ala97Pro
Coding: c.289G>C
MANE Select: NM_207406
dbSNP: rs866025967
Type: single nucleotide variant
Location: chr4:42151855 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.57
Residue 97: the 'disordered' region

Full BEND4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND4 p.Gln224Glu Uncertain significance ★★ ⚠ same type
BEND4 p.Ser268Leu Uncertain significance ★★ ⚠ same type
BEND4 p.Pro473= Likely benign ★★ same type
BEND4 p.Ala125Thr Uncertain significance ★ ⚠ same type
BEND4 p.Ala244Pro Uncertain significance ★ ⚠ same type
BEND4 p.Ala518Pro Uncertain significance ★ ⚠ same type
BEND4 p.Ala66Val Uncertain significance ★ ⚠ same type
BEND4 p.Ala82Pro 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/bend4-p-ala97pro (accessed [today's date]).

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