Is BBS5 p.Arg207Cys (c.619C>T) pathogenic?

BBS5 p.Arg207Cys (c.619C>T) is classified Uncertain significance in BBS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). AlphaMissense: likely benign (0.1449); Very rare (popmax 0.00676%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS5 p.Arg207Cys (c.619C>T)?

BBS5 p.Arg207Cys (c.619C>T) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS5 p.Arg207Cys (c.619C>T) in the general population?

BBS5 p.Arg207Cys (c.619C>T) is very rare (popmax 0.00676%, afr) (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 BBS5 p.Arg207Cys (c.619C>T)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

BBS5 p.Arg207Cys

c.619C>T · rs756421732 · VCV1905699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00676%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -13.28	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.023 · regional, not allelic
Overall
CADD	24.9	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 0.00676% African / African-American · 5/73,976 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00163%

Overall 0.000509% 8/1,570,194 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00676%	14,795
East Asian	0.00225%	44,506
South Asian	0.00223%	44,800

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: BBS5
Protein: p.Arg207Cys
Coding: c.619C>T
MANE Select: NM_152384
dbSNP: rs756421732
Type: single nucleotide variant
Location: chr2:169497627 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 1 PDB
Residue 207: a UniProt-annotated variant site (found as heterozygous variant in patients with bardet-biedl syndrome; might have a modifying effect on disease phenotype)

Full BBS5 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

BBS5 p.Arg207His Benign/Likely benign ★★ ⚠ same residue
BBS5 c.143-1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-2A>G Likely pathogenic ★★ same condition
BBS5 c.522+3A>G Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.681+1G>T Pathogenic/Likely pathogenic ★★ same condition
BBS5 p.Arg138Cys Likely pathogenic ★★ same condition
BBS5 p.Arg138His 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/bbs5-p-arg207cys (accessed [today's date]).

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