Is BEND5 p.Ala63Ser (c.187G>T) pathogenic?

BEND5 p.Ala63Ser (c.187G>T) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-03). AlphaMissense: likely benign (0.0694); Ultra-rare (popmax 0.0224%, mid).

How common is BEND5 p.Ala63Ser (c.187G>T) in the general population?

BEND5 p.Ala63Ser (c.187G>T) is ultra-rare (popmax 0.0224%, mid) (gnomAD).

What do computational predictors say about BEND5 p.Ala63Ser (c.187G>T)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

BEND5 p.Ala63Ser

c.187G>T · rs1645103441 · VCV2228823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0224%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP 0.99, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 200 bp · p 0.41 · regional, not allelic
Overall
CADD	19.99	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 0.0224% Middle Eastern · 1/4,460 alleles

Overall 0.000225% 3/1,333,168 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0224%	4,460
Remaining individualsnot grpmax-eligible	0.00175%	57,024
European (non-Finnish)	8.91e-05%	1,122,168

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.Ala63Ser
Coding: c.187G>T
MANE Select: NM_032785 · reported on NM_024603
dbSNP: rs1645103441
Type: single nucleotide variant
Location: chr1:48776645 (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-ala63ser (accessed [today's date]).

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