Is BBS7 p.Leu550Val (c.1648C>G) pathogenic?

BBS7 p.Leu550Val (c.1648C>G) is classified Uncertain significance in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: ambiguous (0.5547); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS7 p.Leu550Val (c.1648C>G)?

BBS7 p.Leu550Val (c.1648C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BBS7 p.Leu550Val (c.1648C>G) in the general population?

BBS7 p.Leu550Val (c.1648C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS7 p.Leu550Val (c.1648C>G)?

AlphaMissense predicts ambiguous (score 0.5547) — an in-silico prediction, not a clinical call.

BBS7 p.Leu550Val

c.1648C>G · rs2476445369 · VCV3133171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5547 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5547	ambiguous
REVEL	0.646	pathogenic-leaning
SaProt	LLR -12.07	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	23.2	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.Leu550Val
Coding: c.1648C>G
MANE Select: NM_176824
dbSNP: rs2476445369
Type: single nucleotide variant
Location: chr4:121833259 (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-leu550val (accessed [today's date]).

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