Is BBS2 p.Leu93Phe (c.279A>T) pathogenic?

BBS2 p.Leu93Phe (c.279A>T) is classified Uncertain significance in BBS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-26). AlphaMissense: likely benign (0.1264); Absent from gnomAD v4.1.

How common is BBS2 p.Leu93Phe (c.279A>T) in the general population?

BBS2 p.Leu93Phe (c.279A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS2 p.Leu93Phe (c.279A>T)?

AlphaMissense predicts likely benign (score 0.1264) — an in-silico prediction, not a clinical call.

BBS2 p.Leu93Phe

c.279A>T · rs886042185 · VCV281545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1264 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1264	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.55, 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

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.Leu93Phe
Coding: c.279A>T
MANE Select: NM_031885
dbSNP: rs886042185
Type: single nucleotide variant
Location: chr16:56514519 (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

Similar variants

BBS2 p.Leu93Ter Likely pathogenic ★ same residue
BBS2 p.Leu93= Likely benign ★ 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

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-leu93phe (accessed [today's date]).

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