Is BBS2 p.Ile138Ser (c.413T>G) pathogenic?

BBS2 p.Ile138Ser (c.413T>G) is classified Conflicting classifications of pathogenicity in BBS2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2020-01-09). AlphaMissense: ambiguous (0.3599); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with BBS2 p.Ile138Ser (c.413T>G)?

BBS2 p.Ile138Ser (c.413T>G) is associated with retinitis pigmentosa (ClinVar).

How common is BBS2 p.Ile138Ser (c.413T>G) in the general population?

BBS2 p.Ile138Ser (c.413T>G) 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.Ile138Ser (c.413T>G)?

AlphaMissense predicts ambiguous (score 0.3599) — an in-silico prediction, not a clinical call.

BBS2 p.Ile138Ser

c.413T>G · rs1386789664 · VCV623887

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3599 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.3599	ambiguous
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -10.57	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	27.4	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.Ile138Ser
Coding: c.413T>G
MANE Select: NM_031885
dbSNP: rs1386789664
Type: single nucleotide variant
Location: chr16:56511217 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.Arg632Pro Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Asp104Ala Pathogenic ★★ same condition
BBS2 p.Pro134Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
BBS2 p.Tyr24Ter Pathogenic/Likely pathogenic ★★ same condition
BBS2 c.940+3A>C Uncertain significance ★★ same condition
BBS2 p.Ala33Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
BBS2 p.Asn284Ile Uncertain significance ★ ⚠ same condition
BBS2 p.Leu221fs 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-ile138ser (accessed [today's date]).

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