Is BBS7 p.Cys152Ser (c.455G>C) pathogenic?

BBS7 p.Cys152Ser (c.455G>C) is classified Uncertain significance in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: ambiguous (0.3402); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS7 p.Cys152Ser (c.455G>C)?

BBS7 p.Cys152Ser (c.455G>C) is associated with Inborn genetic diseases (ClinVar).

How common is BBS7 p.Cys152Ser (c.455G>C) in the general population?

BBS7 p.Cys152Ser (c.455G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS7 p.Cys152Ser (c.455G>C)?

AlphaMissense predicts ambiguous (score 0.3402) — an in-silico prediction, not a clinical call.

BBS7 p.Cys152Ser

c.455G>C · VCV3990805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3402 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3402	ambiguous
REVEL	0.484	indeterminate
SaProt	LLR -7.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	23.0	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: BBS7
Protein: p.Cys152Ser
Coding: c.455G>C
MANE Select: NM_176824
Type: single nucleotide variant
Location: chr4:121859065 (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.Cys152Arg Uncertain significance ★ ⚠ same residue
BBS7 p.Cys152Phe Uncertain significance ★ ⚠ same residue
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

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-cys152ser (accessed [today's date]).

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