Is BEND7 p.Pro228Arg (c.683C>G) pathogenic?

BEND7 p.Pro228Arg (c.683C>G) is classified Uncertain significance in BEND7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). Very rare (popmax 0.00127%, nfe).

How common is BEND7 p.Pro228Arg (c.683C>G) in the general population?

BEND7 p.Pro228Arg (c.683C>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

BEND7 p.Pro228Arg

c.683C>G · VCV3260796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.153	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,882 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00118% 19/1,613,246 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,341
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)grpmax	0.00127%	78,659

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro228Arg
Coding: c.683C>G
MANE Select: NM_001369863
Type: single nucleotide variant
Location: chr10:13492765 (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.Pro228Ser 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-pro228arg (accessed [today's date]).

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