Is BBS10 p.Ser358Pro (c.1072T>C) pathogenic?

BBS10 p.Ser358Pro (c.1072T>C) is classified Uncertain significance in BBS10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-20). AlphaMissense: likely benign (0.0774); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with BBS10 p.Ser358Pro (c.1072T>C)?

BBS10 p.Ser358Pro (c.1072T>C) is associated with Inborn genetic diseases, Bardet-Biedl syndrome (ClinVar).

How common is BBS10 p.Ser358Pro (c.1072T>C) in the general population?

BBS10 p.Ser358Pro (c.1072T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BBS10 p.Ser358Pro (c.1072T>C)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

BBS10 p.Ser358Pro

c.1072T>C · rs748933585 · VCV2415979

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -6.94	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 2.9	GERP 0.49, phastCons 0.95
Regional constraint	o/e 1.00	unconstrained · MANE · 2,542 bp · p 1 · regional, not allelic
Overall
CADD	15.99	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 0.0165% Middle Eastern · 1/6,060 alleles

Overall 0.000205% 3/1,460,240 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Admixed American	0.00167%	60,024
European (non-Finnish)	8.47e-05%	1,180,026

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.Ser358Pro
Coding: c.1072T>C
MANE Select: NM_024685
dbSNP: rs748933585
Type: single nucleotide variant
Location: chr12:76346913 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome

Similar variants

BBS10 p.Ser358= Likely benign ★★ same residue
BBS10 p.Ser358fs 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

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-ser358pro (accessed [today's date]).

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