Is BBS7 p.Phe429Val (c.1285T>G) pathogenic?

BBS7 p.Phe429Val (c.1285T>G) is classified Uncertain significance in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-23). AlphaMissense: likely benign (0.1803); Very rare (popmax 8.53e-05%, nfe).

How common is BBS7 p.Phe429Val (c.1285T>G) in the general population?

BBS7 p.Phe429Val (c.1285T>G) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about BBS7 p.Phe429Val (c.1285T>G)?

AlphaMissense predicts likely benign (score 0.1803) — an in-silico prediction, not a clinical call.

BBS7 p.Phe429Val

c.1285T>G · rs149880614 · VCV430210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1803	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -10.53	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,171,676 alleles

Overall 6.9e-05% 1/1,449,320 alleles · very rare

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: BBS7
Protein: p.Phe429Val
Coding: c.1285T>G
MANE Select: NM_176824
dbSNP: rs149880614
Type: single nucleotide variant
Location: chr4:121843947 (GRCh38)
Gene constraint: LOEUF 0.701 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.99

Full BBS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BBS7 p.Phe429= Likely benign ★ same residue
BBS7 c.1305+2T>A Likely pathogenic ★★ same type
BBS7 c.1371+1G>A Likely pathogenic ★★ same type
BBS7 c.1512-1G>A Likely pathogenic ★★ same type
BBS7 c.1677-2A>G Pathogenic/Likely pathogenic ★★ same type
BBS7 c.1891-2A>C Pathogenic/Likely pathogenic ★★ same type
BBS7 c.342-2A>G Pathogenic/Likely pathogenic ★★ same type
BBS7 c.529-2A>G Pathogenic/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/bbs7-p-phe429val (accessed [today's date]).

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