Is BBS7 p.Ala425Val (c.1274C>T) pathogenic?

BBS7 p.Ala425Val (c.1274C>T) is classified Uncertain significance in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.744); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS7 p.Ala425Val (c.1274C>T)?

BBS7 p.Ala425Val (c.1274C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BBS7 p.Ala425Val (c.1274C>T) in the general population?

BBS7 p.Ala425Val (c.1274C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS7 p.Ala425Val (c.1274C>T)?

AlphaMissense predicts likely pathogenic (score 0.744) — an in-silico prediction, not a clinical call.

BBS7 p.Ala425Val

c.1274C>T · rs2476490418 · VCV2490842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.744 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,306)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.744	likely pathogenic
REVEL	0.585	indeterminate
SaProt	LLR -13.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.36	donor loss, 31 bp away · masked 0 · deltas
Pangolin	Δ0.42	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,602,306). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BBS7
Protein: p.Ala425Val
Coding: c.1274C>T
MANE Select: NM_176824
dbSNP: rs2476490418
Type: single nucleotide variant
Location: chr4:121843958 (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

Disease context

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

Similar variants

BBS7 p.Gln339Ter Pathogenic ★★ same condition
BBS7 p.Arg160Cys Uncertain significance ★★ ⚠ same condition
BBS7 p.Arg170Gly Uncertain significance ★★ ⚠ same condition
BBS7 p.Arg228Cys Uncertain significance ★★ ⚠ same condition
BBS7 p.Arg459Cys Uncertain significance ★★ ⚠ same condition
BBS7 p.Arg459His Uncertain significance ★★ ⚠ same condition
BBS7 p.Arg496Ile Uncertain significance ★★ ⚠ same condition
BBS7 p.Arg496Lys 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/bbs7-p-ala425val (accessed [today's date]).

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