BEND7 p.Pro223Ser
c.667C>T · VCV4645775
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00263%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.07 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic |
| Overall | ||
| CADD | 17.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00263%
European (non-Finnish) · 31/1,178,988 alleles
Filtering AF
0.00188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.00199%
32/1,609,034 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00263% | 38,032 |
| African / African-American | 0.00135% | 74,282 |
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.Pro223Ser
- Coding
- c.667C>T
- MANE Select
- NM_001369863
- Type
- single nucleotide variant
- Location
- chr10:13492781 (GRCh38)
- Gene constraint
- LOEUF 0.842 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.17
- Residue 223
- the 'disordered' region
Similar variants
- 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
- BEND7 p.Arg136Gly 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-pro223ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown