Is BBS7 p.Ser574Cys (c.1721C>G) pathogenic?

BBS7 p.Ser574Cys (c.1721C>G) is classified Uncertain significance in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-25). AlphaMissense: ambiguous (0.485); Very rare (popmax 0.00535%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS7 p.Ser574Cys (c.1721C>G)?

BBS7 p.Ser574Cys (c.1721C>G) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS7 p.Ser574Cys (c.1721C>G) in the general population?

BBS7 p.Ser574Cys (c.1721C>G) is very rare (popmax 0.00535%, nfe) (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 BBS7 p.Ser574Cys (c.1721C>G)?

AlphaMissense predicts ambiguous (score 0.485) — an in-silico prediction, not a clinical call.

BBS7 p.Ser574Cys

c.1721C>G · rs765782762 · VCV1407943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.485 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.485	ambiguous
REVEL	0.684	pathogenic-leaning
SaProt	LLR -11.76	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.29	acceptor loss, 12 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.00535% European (non-Finnish) · 63/1,176,890 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00389%

Overall 0.00398% 64/1,608,664 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00535%	18,681
African / African-American	0.00134%	74,754

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: BBS7
Protein: p.Ser574Cys
Coding: c.1721C>G
MANE Select: NM_176824
dbSNP: rs765782762
Type: single nucleotide variant
Location: chr4:121828684 (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

Bardet-Biedl syndrome — 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

BBS7 c.1305+2T>A Likely pathogenic ★★ same condition
BBS7 c.1371+1G>A Likely pathogenic ★★ same condition
BBS7 c.1512-1G>A Likely pathogenic ★★ same condition
BBS7 c.1677-2A>G Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.1891-2A>C Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.342-2A>G Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.849+1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS7 p.Arg280Ter 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/bbs7-p-ser574cys (accessed [today's date]).

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