Is BEND4 p.Ser72Arg (c.214A>C) pathogenic?

BEND4 p.Ser72Arg (c.214A>C) is classified Uncertain significance in BEND4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: likely pathogenic (0.8425); Very rare (popmax 0.00852%, amr).

How common is BEND4 p.Ser72Arg (c.214A>C) in the general population?

BEND4 p.Ser72Arg (c.214A>C) is very rare (popmax 0.00852%, amr) (gnomAD).

What do computational predictors say about BEND4 p.Ser72Arg (c.214A>C)?

AlphaMissense predicts likely pathogenic (score 0.8425) — an in-silico prediction, not a clinical call.

BEND4 p.Ser72Arg

c.214A>C · VCV3480426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00852%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8425	likely pathogenic
REVEL	0.105	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.81, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 35 kb · p 0.85 · regional, not allelic
Overall
CADD	19.79	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 0.00852% Admixed American · 2/23,480 alleles

Filtering AF 0.00151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000627%

Overall 0.000239% 3/1,252,842 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00852%	11,740
Remaining individualsnot grpmax-eligible	0.00217%	46,168

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: BEND4
Protein: p.Ser72Arg
Coding: c.214A>C
MANE Select: NM_207406
Type: single nucleotide variant
Location: chr4:42151930 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.57
Residue 72: 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-ser72arg (accessed [today's date]).

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