Is BVES p.Phe244fs (c.731_734del) pathogenic?

BVES p.Phe244fs (c.731734del) is classified Likely pathogenic in BVES (ClinVar, Single submitter, 1 submitter; last evaluated 2016-11-08). Very rare (popmax 0.00212%, nfe).

How common is BVES p.Phe244fs (c.731_734del) in the general population?

BVES p.Phe244fs (c.731_734del) is very rare (popmax 0.00212%, nfe) (gnomAD).

BVES p.Phe244fs

c.731_734del · rs759745220 · VCV377143

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -10	GERP -5.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,179,330 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,612,518 alleles · very rare exomes 27/1,460,316 · genomes 0/152,202 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,233
European (non-Finnish)grpmax	0.00212%	47,173

Remaining individuals 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: BVES
Protein: p.Phe244fs
Coding: c.731_734del
MANE Select: NM_001199563
dbSNP: rs759745220
Type: Deletion
Location: chr6:105116783 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.08

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

Similar variants

POP1 p.Leu244= Likely benign ★ same residue
POP1 p.Asp511fs Pathogenic ★ same type
POP1 p.Gly506fs Pathogenic ★ same type
POP1 p.Ile272fs Pathogenic ★ same type
POP1 p.Lys299fs Pathogenic ★ same type
POP1 p.Ser116fs Pathogenic ★ same type
POP1 p.Thr752fs Pathogenic ★ same type
POPDC1 c.351+1del Likely pathogenic ★ 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/bves-p-phe244fs (accessed [today's date]).

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