Is BEND7 p.Pro228Ser (c.682C>T) pathogenic?

BEND7 p.Pro228Ser (c.682C>T) is classified Uncertain significance in BEND7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-06). Rare (popmax 0.178%, afr).

How common is BEND7 p.Pro228Ser (c.682C>T) in the general population?

BEND7 p.Pro228Ser (c.682C>T) is rare (popmax 0.178%, afr) (gnomAD).

BEND7 p.Pro228Ser

c.682C>T · rs144230873 · VCV2458721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.178%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.134	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 0.15, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.178% African / African-American · 133/74,878 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.144%

Overall 0.00887% 143/1,612,998 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.178%	563
Middle Eastern	0.0165%	6,060
Admixed American	0.0118%	8,503
Remaining individualsnot grpmax-eligible	0.0032%	31,223

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: BEND7
Protein: p.Pro228Ser
Coding: c.682C>T
MANE Select: NM_001369863
dbSNP: rs144230873
Type: single nucleotide variant
Location: chr10:13492766 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.17
Residue 228: the 'disordered' region

Full BEND7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND7 p.Pro228Arg Uncertain significance ★ same residue
BEND7 p.Ala103Val Uncertain significance ★ same type
BEND7 p.Ala105Asp Uncertain significance ★ same type
BEND7 p.Ala105Val Uncertain significance ★ same type
BEND7 p.Ala255Gly Uncertain significance ★ same type
BEND7 p.Ala397Val Uncertain significance ★ same type
BEND7 p.Arg114Cys Uncertain significance ★ same type
BEND7 p.Arg134Cys 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/bend7-p-pro228ser (accessed [today's date]).

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