Is BBS10 p.Ala14= (c.42G>A) pathogenic?

BBS10 p.Ala14= (c.42G>A) is classified Likely benign in BBS10 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-18). Very rare (popmax 0.00543%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS10 p.Ala14= (c.42G>A)?

BBS10 p.Ala14= (c.42G>A) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS10 p.Ala14= (c.42G>A) in the general population?

BBS10 p.Ala14= (c.42G>A) is very rare (popmax 0.00543%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS10 p.Ala14=

c.42G>A · rs373458861 · VCV310499

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00543%, nfe)

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 -3.5	GERP -2.4
Overall
CADD	8.613	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00543% European (non-Finnish) · 64/1,178,048 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00422% 68/1,609,562 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00543%	18,407
Remaining individualsnot grpmax-eligible	0.00321%	31,138
African / African-American	0.00134%	74,842
South Asian	0.00111%	90,434

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.Ala14=
Coding: c.42G>A
MANE Select: NM_024685
dbSNP: rs373458861
Type: single nucleotide variant
Location: chr12:76348317 (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.Ala14fs Pathogenic ★★ 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-ala14 (accessed [today's date]).

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