Is BBS10 p.Pro575fs (c.1724del) pathogenic?

BBS10 p.Pro575fs (c.1724del) is classified Pathogenic/Likely pathogenic in BBS10 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). Very rare (popmax 8.48e-05%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS10 p.Pro575fs (c.1724del)?

BBS10 p.Pro575fs (c.1724del) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 10 (ClinVar).

How common is BBS10 p.Pro575fs (c.1724del) in the general population?

BBS10 p.Pro575fs (c.1724del) is very rare (popmax 8.48e-05%, 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.Pro575fs

c.1724del · rs1057516754 · VCV370772

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.35	GERP -3.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,322 alleles

Overall 6.2e-05% 1/1,612,760 alleles · very rare exomes 1/1,460,396 · genomes 0/152,364 · 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.Pro575fs
Coding: c.1724del
MANE Select: NM_024685
dbSNP: rs1057516754
Type: Deletion
Location: chr12:76346261 (GRCh38)
Gene constraint: LOEUF 1.418 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.26
Residue 575: 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.Pro575Leu Uncertain significance ★ ⚠ same residue
BBS10 p.Pro575= Likely benign ★ same residue
BBS10 p.Ala14fs Pathogenic ★★ same condition
BBS10 p.Arg467fs Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Asn364fs Pathogenic ★★ same condition
BBS10 p.Asn605fs Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Asp412fs Pathogenic/Likely pathogenic ★★ same condition
BBS10 p.Asp515fs 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-pro575fs (accessed [today's date]).

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