Is BBS10 p.Ser335= (c.1005A>G) pathogenic?

BBS10 p.Ser335= (c.1005A>G) is classified Likely benign in BBS10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-14). Ultra-rare (popmax 0.0165%, mid); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS10 p.Ser335= (c.1005A>G)?

BBS10 p.Ser335= (c.1005A>G) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS10 p.Ser335= (c.1005A>G) in the general population?

BBS10 p.Ser335= (c.1005A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

BBS10 p.Ser335=

c.1005A>G · rs2540956258 · VCV3021634

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.054	GERP -0.95, phastCons 0.002
Overall
CADD	5.865	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000124% 2/1,611,346 alleles · ultra-rare exomes 2/1,458,992 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	8.47e-05%	1,179,986

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.Ser335=
Coding: c.1005A>G
MANE Select: NM_024685
dbSNP: rs2540956258
Type: single nucleotide variant
Location: chr12:76346980 (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 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
BBS10 p.Gln192Ter 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/bbs10-p-ser335 (accessed [today's date]).

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