Is BBS12 p.Val2Ala (c.5T>C) pathogenic?

BBS12 p.Val2Ala (c.5T>C) is classified Uncertain significance in BBS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). AlphaMissense: likely benign (0.1275); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS12 p.Val2Ala (c.5T>C)?

BBS12 p.Val2Ala (c.5T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BBS12 p.Val2Ala (c.5T>C) in the general population?

BBS12 p.Val2Ala (c.5T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS12 p.Val2Ala (c.5T>C)?

AlphaMissense predicts likely benign (score 0.1275) — an in-silico prediction, not a clinical call.

BBS12 p.Val2Ala

c.5T>C · rs2485071378 · VCV2214951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1275 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1275	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.28	GERP -3.5, phastCons 0.016
Regional constraint	o/e 0.90	unconstrained · MANE · 2,129 bp · p 0.0042 · regional, not allelic
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: BBS12
Protein: p.Val2Ala
Coding: c.5T>C
MANE Select: NM_152618
dbSNP: rs2485071378
Type: single nucleotide variant
Location: chr4:122741897 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.92

Full BBS12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BBS12 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
BBS12 p.Ala448Val Uncertain significance ★★ ⚠ same condition
BBS12 p.Ala510Thr Uncertain significance ★★ ⚠ same condition
BBS12 p.Arg239Lys Uncertain significance ★★ ⚠ same condition
BBS12 p.Arg421Ser Uncertain significance ★★ ⚠ same condition
BBS12 p.Arg487Gly Uncertain significance ★★ ⚠ same condition
BBS12 p.Arg55Ser Uncertain significance ★★ same condition
BBS12 p.Asp463Gly Uncertain significance ★★ ⚠ 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/bbs12-p-val2ala (accessed [today's date]).

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