Is BBS10 p.Ser3Arg (c.7A>C) pathogenic?

BBS10 p.Ser3Arg (c.7A>C) is classified Uncertain significance in BBS10 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-27). AlphaMissense: likely benign (0.1356); Very rare (popmax 0.000515%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS10 p.Ser3Arg (c.7A>C)?

BBS10 p.Ser3Arg (c.7A>C) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS10 p.Ser3Arg (c.7A>C) in the general population?

BBS10 p.Ser3Arg (c.7A>C) is very rare (popmax 0.000515%, 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 BBS10 p.Ser3Arg (c.7A>C)?

AlphaMissense predicts likely benign (score 0.1356) — an in-silico prediction, not a clinical call.

BBS10 p.Ser3Arg

c.7A>C · rs1396450993 · VCV1375630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1356 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000515%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.1356	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -2.6
Regional constraint	o/e 1.00	unconstrained · MANE · 2,542 bp · p 1 · regional, not allelic
Overall
CADD	0.382	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 0.000515% European (non-Finnish) · 6/1,165,906 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000378% 6/1,586,182 alleles · very rare exomes 5/1,434,066 · genomes 1/152,116 · joint denominator

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.Ser3Arg
Coding: c.7A>C
MANE Select: NM_024685
dbSNP: rs1396450993
Type: single nucleotide variant
Location: chr12:76348352 (GRCh38)
Gene constraint: LOEUF 1.418 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.26

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

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.Ser3fs Pathogenic/Likely pathogenic ★★ same residue
BBS10 p.Ser3_Met5delinsArg Conflicting classifications of pathogenicity ★ 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

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-ser3arg (accessed [today's date]).

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