Is BEND5 p.Ser279Leu (c.836C>T) pathogenic?

BEND5 p.Ser279Leu (c.836C>T) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: ambiguous (0.4657); Very rare (popmax 0.00111%, sas).

How common is BEND5 p.Ser279Leu (c.836C>T) in the general population?

BEND5 p.Ser279Leu (c.836C>T) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about BEND5 p.Ser279Leu (c.836C>T)?

AlphaMissense predicts ambiguous (score 0.4657) — an in-silico prediction, not a clinical call.

BEND5 p.Ser279Leu

c.836C>T · VCV4205566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4657	ambiguous
REVEL	0.255	benign-leaning
SaProt	LLR -8.70	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 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.01 · regional, not allelic
Overall
CADD	27.6	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 0.00111% South Asian · 1/90,428 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,458,858 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,428
European (non-Finnish)	0.00017%	589,289

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.Ser279Leu
Coding: c.836C>T
MANE Select: NM_032785 · reported on NM_024603
Type: single nucleotide variant
Location: chr1:48742681 (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-ser279leu (accessed [today's date]).

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