Is BBS10 p.Asp515= (c.1545T>C) pathogenic?

BBS10 p.Asp515= (c.1545T>C) is classified Benign in BBS10 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Common (popmax 7.18%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Bardet-Biedl syndrome.

What condition is associated with BBS10 p.Asp515= (c.1545T>C)?

BBS10 p.Asp515= (c.1545T>C) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 10 (ClinVar).

How is Bardet-Biedl syndrome inherited?

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

BBS10 p.Asp515=

Q: How common is BBS10 p.Asp515= (c.1545T>C) in the general population?

BBS10 p.Asp515= (c.1545T>C) is common (popmax 7.18%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1545T>C · rs77565309 · VCV261754

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 7.18%, eas) — too common for a highly-penetrant pathogenic allele

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 2.4	GERP 1.6, phastCons 0.005
Overall
CADD	3.386	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.18% East Asian · 3,222/44,870 alleles

Filtering AF 6.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.89%

Overall 0.226% 3,644/1,614,148 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.18%	14
Ashkenazi Jewishnot grpmax-eligible	0.169%	592
Remaining individualsnot grpmax-eligible	0.158%	631
South Asian	0.139%	717
Middle Eastern	0.033%	3,031
Finnishnot grpmax-eligible	0.0187%	5,336
European (non-Finnish)	0.0108%	9,219
Admixed American	0.00666%	15,008

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.Asp515=
Coding: c.1545T>C
MANE Select: NM_024685
dbSNP: rs77565309
Type: single nucleotide variant
Location: chr12:76346440 (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

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.Asp515fs Pathogenic/Likely 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-asp515 (accessed [today's date]).

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