Is BEND4 p.Arg165Gln (c.494G>A) pathogenic?

BEND4 p.Arg165Gln (c.494G>A) is classified Uncertain significance in BEND4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: ambiguous (0.4959); Ultra-rare (popmax 0.0344%, sas).

How common is BEND4 p.Arg165Gln (c.494G>A) in the general population?

BEND4 p.Arg165Gln (c.494G>A) is ultra-rare (popmax 0.0344%, sas) (gnomAD).

What do computational predictors say about BEND4 p.Arg165Gln (c.494G>A)?

AlphaMissense predicts ambiguous (score 0.4959) — an in-silico prediction, not a clinical call.

BEND4 p.Arg165Gln

c.494G>A · rs200387125 · VCV2333067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4959 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0344%, sas)

Computational evidence

Protein change
AlphaMissense	0.4959	ambiguous
REVEL	0.35	indeterminate
SaProt	LLR -6.60	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 35 kb · p 0.85 · regional, not allelic
Overall
CADD	26.9	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 0.0344% South Asian · 28/81,502 alleles

Filtering AF 0.0244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.0177% 279/1,572,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0344%	2,911
Finnishnot grpmax-eligible	0.0241%	4,152
European (non-Finnish)	0.0193%	5,191
Remaining individualsnot grpmax-eligible	0.0131%	7,608
Admixed American	0.0075%	13,325

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.Arg165Gln
Coding: c.494G>A
MANE Select: NM_207406
dbSNP: rs200387125
Type: single nucleotide variant
Location: chr4:42143988 (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-arg165gln (accessed [today's date]).

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