Is BBS2 p.Thr397Ile (c.1190C>T) pathogenic?

BBS2 p.Thr397Ile (c.1190C>T) is classified Uncertain significance in BBS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1; Associated with retinitis pigmentosa 74.

What condition is associated with BBS2 p.Thr397Ile (c.1190C>T)?

BBS2 p.Thr397Ile (c.1190C>T) is associated with retinitis pigmentosa 74, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Thr397Ile (c.1190C>T) in the general population?

BBS2 p.Thr397Ile (c.1190C>T) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about BBS2 p.Thr397Ile (c.1190C>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

BBS2 p.Thr397Ile

c.1190C>T · rs368138622 · VCV1384369

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 74

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.43	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 5.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	17.85	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

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.Thr397Ile
Coding: c.1190C>T
MANE Select: NM_031885
dbSNP: rs368138622
Type: single nucleotide variant
Location: chr16:56501388 (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

retinitis pigmentosa 74 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 2 Bardet-Biedl syndrome

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

BBS2 p.Thr397Ser Uncertain significance ★★ ⚠ same residue
OGFOD1 p.Pro397Ser Likely benign ★ same residue
BBS2 c.118-1G>T Likely pathogenic ★★ same condition
BBS2 c.118-2A>C Likely pathogenic ★★ same condition
BBS2 c.118-2A>G Likely pathogenic ★★ same condition
BBS2 c.1225+2T>C Likely pathogenic ★★ same condition
BBS2 c.1225+2T>G Likely pathogenic ★★ same condition
BBS2 c.1397+1G>A 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/bbs2-p-thr397ile (accessed [today's date]).

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