Is BBS7 p.Arg484Cys (c.1450C>T) pathogenic?

BBS7 p.Arg484Cys (c.1450C>T) is classified Uncertain significance in BBS7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-22). AlphaMissense: likely benign (0.078); Ultra-rare (popmax 0.0164%, mid); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS7 p.Arg484Cys (c.1450C>T)?

BBS7 p.Arg484Cys (c.1450C>T) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 7 (ClinVar).

How common is BBS7 p.Arg484Cys (c.1450C>T) in the general population?

BBS7 p.Arg484Cys (c.1450C>T) is ultra-rare (popmax 0.0164%, mid) (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.Arg484Cys (c.1450C>T)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

BBS7 p.Arg484Cys

c.1450C>T · rs747889031 · VCV1403412

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.506	indeterminate
SaProt	LLR -13.03	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP -0.13, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	24.3	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000991% 16/1,613,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00134%	74,876
South Asian	0.0011%	91,076
European (non-Finnish)	0.00102%	98,321

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.Arg484Cys
Coding: c.1450C>T
MANE Select: NM_176824
dbSNP: rs747889031
Type: single nucleotide variant
Location: chr4:121835205 (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

Also linked: Bardet-Biedl syndrome 7

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS7 p.Arg484His Uncertain significance ★ ⚠ same residue
BBS7 p.Arg484Pro Uncertain significance ★ ⚠ same residue
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

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-arg484cys (accessed [today's date]).

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