Is BEND4 p.Ser155Arg (c.465C>A) pathogenic?

BEND4 p.Ser155Arg (c.465C>A) is classified Uncertain significance in BEND4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2698); Ultra-rare (popmax 0.0322%, afr).

How common is BEND4 p.Ser155Arg (c.465C>A) in the general population?

BEND4 p.Ser155Arg (c.465C>A) is ultra-rare (popmax 0.0322%, afr) (gnomAD).

What do computational predictors say about BEND4 p.Ser155Arg (c.465C>A)?

AlphaMissense predicts likely benign (score 0.2698) — an in-silico prediction, not a clinical call.

BEND4 p.Ser155Arg

c.465C>A · VCV4205412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2698 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0322%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2698	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.39	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 3	GERP 0.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 35 kb · p 0.85 · regional, not allelic
Overall
CADD	18.2	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 0.0322% African / African-American · 22/68,220 alleles

Filtering AF 0.0217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0183%

Overall 0.00266% 40/1,505,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0322%	3,101
European (non-Finnish)	0.00159%	62,801

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.Ser155Arg
Coding: c.465C>A
MANE Select: NM_207406
Type: single nucleotide variant
Location: chr4:42151679 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.57

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-ser155arg (accessed [today's date]).

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