Is BBS2 p.Ile238Ser (c.713T>G) pathogenic?

BBS2 p.Ile238Ser (c.713T>G) is classified Uncertain significance in BBS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.989); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS2 p.Ile238Ser (c.713T>G)?

BBS2 p.Ile238Ser (c.713T>G) is associated with Inborn genetic diseases (ClinVar).

How common is BBS2 p.Ile238Ser (c.713T>G) in the general population?

BBS2 p.Ile238Ser (c.713T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS2 p.Ile238Ser (c.713T>G)?

AlphaMissense predicts likely pathogenic (score 0.989) — an in-silico prediction, not a clinical call.

BBS2 p.Ile238Ser

c.713T>G · VCV4595067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.989	likely pathogenic · top 3% in BBS2
REVEL	0.703	pathogenic-leaning
SaProt	LLR -14.16	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Ile238Ser
Coding: c.713T>G
MANE Select: NM_031885
Type: single nucleotide variant
Location: chr16:56506124 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49

Full BBS2 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

Similar variants

BBS2 p.Ala682Thr Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg353Cys Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg374Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg539Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg622Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg661His Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg684His Uncertain significance ★★ ⚠ same condition
BBS2 p.Asp616Val Uncertain significance ★★ ⚠ 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/bbs2-p-ile238ser (accessed [today's date]).

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