Is BBS10 p.Val331Ala (c.992T>C) pathogenic?

BBS10 p.Val331Ala (c.992T>C) is classified Conflicting classifications of pathogenicity in BBS10 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-19). AlphaMissense: likely benign (0.2986); Very rare (popmax 0.00133%, afr); Associated with Bardet-Biedl syndrome 10.

What condition is associated with BBS10 p.Val331Ala (c.992T>C)?

BBS10 p.Val331Ala (c.992T>C) is associated with Bardet-Biedl syndrome 10 (ClinVar).

How common is BBS10 p.Val331Ala (c.992T>C) in the general population?

BBS10 p.Val331Ala (c.992T>C) is very rare (popmax 0.00133%, afr) (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 BBS10 p.Val331Ala (c.992T>C)?

AlphaMissense predicts likely benign (score 0.2986) — an in-silico prediction, not a clinical call.

BBS10 p.Val331Ala

c.992T>C · rs2540956270 · VCV2679978

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome 10

Computational evidence

Protein change
AlphaMissense	0.2986	likely benign
REVEL	0.863	moderately pathogenic-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
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 1.00	unconstrained · MANE · 2,542 bp · p 1 · regional, not allelic
Overall
CADD	24.7	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 0.00133% African / African-American · 1/75,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,459,416 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,032
European (non-Finnish)	0.000169%	589,984

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: BBS10
Protein: p.Val331Ala
Coding: c.992T>C
MANE Select: NM_024685
dbSNP: rs2540956270
Type: single nucleotide variant
Location: chr12:76346993 (GRCh38)
Gene constraint: LOEUF 1.418 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.26

Full BBS10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS10 c.197+1G>T Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Arg256Ter Pathogenic ★★ same condition
BBS10 p.Arg49Leu Likely pathogenic ★★ ⚠ same condition
BBS10 p.Arg49Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
BBS10 p.Cys28Ter Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Cys91Trp Pathogenic ★★ ⚠ same condition
BBS10 p.Gln192Ter Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Gln265Ter Pathogenic/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/bbs10-p-val331ala (accessed [today's date]).

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