Is BBS10 p.Arg660Ser (c.1980A>T) pathogenic?

BBS10 p.Arg660Ser (c.1980A>T) is classified Uncertain significance in BBS10 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-08-01). AlphaMissense: likely benign (0.2135); Very rare (popmax 0.00267%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS10 p.Arg660Ser (c.1980A>T)?

BBS10 p.Arg660Ser (c.1980A>T) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 10 (ClinVar).

How common is BBS10 p.Arg660Ser (c.1980A>T) in the general population?

BBS10 p.Arg660Ser (c.1980A>T) is very rare (popmax 0.00267%, 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 BBS10 p.Arg660Ser (c.1980A>T)?

AlphaMissense predicts likely benign (score 0.2135) — an in-silico prediction, not a clinical call.

BBS10 p.Arg660Ser

c.1980A>T · rs747395215 · VCV2062774

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2135 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.2135	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.69	GERP 0.41, phastCons 0.018
Regional constraint	o/e 1.00	unconstrained · MANE · 2,542 bp · p 1 · regional, not allelic
Overall
CADD	13.59	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,230 alleles · very rare

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: BBS10
Protein: p.Arg660Ser
Coding: c.1980A>T
MANE Select: NM_024685
dbSNP: rs747395215
Type: single nucleotide variant
Location: chr12:76346005 (GRCh38)
Gene constraint: LOEUF 1.418 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.26
Residue 660: a UniProt-annotated variant site (in bbs10; uncertain significance)

Full BBS10 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 10

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS10 p.Arg660= Likely benign ★ same residue
BBS10 c.197+1G>T Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Arg256Ter Pathogenic ★★ same condition
BBS10 p.Arg49Leu Likely pathogenic ★★ ⚠ same condition
BBS10 p.Arg49Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
BBS10 p.Cys28Ter Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Cys91Trp Pathogenic ★★ ⚠ same condition
BBS10 p.Gln137Ter 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/bbs10-p-arg660ser (accessed [today's date]).

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