Is BBS2 p.Tyr317Ser (c.950A>C) pathogenic?

BBS2 p.Tyr317Ser (c.950A>C) is classified Likely pathogenic in BBS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). AlphaMissense: likely pathogenic (0.9616); Absent from gnomAD v4.1.

How common is BBS2 p.Tyr317Ser (c.950A>C) in the general population?

BBS2 p.Tyr317Ser (c.950A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS2 p.Tyr317Ser (c.950A>C)?

AlphaMissense predicts likely pathogenic (score 0.9616) — an in-silico prediction, not a clinical call.

BBS2 p.Tyr317Ser

c.950A>C · rs1597016660 · VCV2498666

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9616 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9616	likely pathogenic ✓ concordant with ClinVar · top 7% in BBS2
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -16.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BBS2
Protein: p.Tyr317Ser
Coding: c.950A>C
MANE Select: NM_031885
dbSNP: rs1597016660
Type: single nucleotide variant
Location: chr16:56502447 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49
Residue 317: a UniProt-annotated variant site (in bbs2)

Full BBS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BBS2 p.Tyr317Cys Pathogenic/Likely pathogenic ★★ same residue
BBS2 c.118-1G>T Likely pathogenic ★★ same type
BBS2 c.118-2A>C Likely pathogenic ★★ same type
BBS2 c.118-2A>G Likely pathogenic ★★ same type
BBS2 c.1225+2T>C Likely pathogenic ★★ same type
BBS2 c.1225+2T>G Likely pathogenic ★★ same type
BBS2 c.1397+1G>A Pathogenic/Likely pathogenic ★★ same type
BBS2 c.1397+2T>C Likely pathogenic ★★ same type

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/bbs2-p-tyr317ser (accessed [today's date]).

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