Is BEND7 p.Ser299Phe (c.896C>T) pathogenic?

BEND7 p.Ser299Phe (c.896C>T) is classified Uncertain significance in BEND7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). Very rare (popmax 0.0061%, nfe).

How common is BEND7 p.Ser299Phe (c.896C>T) in the general population?

BEND7 p.Ser299Phe (c.896C>T) is very rare (popmax 0.0061%, nfe) (gnomAD).

BEND7 p.Ser299Phe

c.896C>T · VCV3480449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0061%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.36	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0061% European (non-Finnish) · 72/1,180,010 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00459% 74/1,613,944 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0061%	16,389
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00134%	74,898

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.Ser299Phe
Coding: c.896C>T
MANE Select: NM_001369863
Type: single nucleotide variant
Location: chr10:13481066 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.17
Residue 299: the ben domain

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

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-ser299phe (accessed [today's date]).

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