Is BBS9 p.Val417Phe (c.1249G>T) pathogenic?

BBS9 p.Val417Phe (c.1249G>T) is classified Uncertain significance in BBS9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-29). AlphaMissense: ambiguous (0.5013); Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome 9.

What condition is associated with BBS9 p.Val417Phe (c.1249G>T)?

BBS9 p.Val417Phe (c.1249G>T) is associated with Bardet-Biedl syndrome 9, Bardet-Biedl syndrome (ClinVar).

How common is BBS9 p.Val417Phe (c.1249G>T) in the general population?

BBS9 p.Val417Phe (c.1249G>T) is absent from gnomAD v4.1 (gnomAD).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BBS9 p.Val417Phe (c.1249G>T)?

AlphaMissense predicts ambiguous (score 0.5013) — an in-silico prediction, not a clinical call.

BBS9 p.Val417Phe

c.1249G>T · rs751604593 · VCV849613

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5013 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Bardet-Biedl syndrome 9

Computational evidence

Protein change
AlphaMissense	0.5013	ambiguous
REVEL	0.508	indeterminate
SaProt	LLR -11.32	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 459 kb · p 0.062 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BBS9
Protein: p.Val417Phe
Coding: c.1249G>T
MANE Select: NM_198428
dbSNP: rs751604593
Type: single nucleotide variant
Location: chr7:33340947 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 2 PDB

Full BBS9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS9 p.Val417Leu Uncertain significance ★ same residue
BBS9 p.Val417Ile Uncertain significance ⚠ same residue
BBS9 c.1329+1738C>T Likely pathogenic ★★ same condition
BBS9 c.1552+2T>A Likely pathogenic ★★ same condition
BBS9 c.1693+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.1789+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.1789+1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS9 c.2299-2A>C Likely pathogenic ★★ same condition

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/bbs9-p-val417phe (accessed [today's date]).

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