Is BBS2 p.Ala122fs (c.365_369delinsTCCTTTTACTTTTCTTAG) pathogenic?

BBS2 p.Ala122fs (c.365369delinsTCCTTTTACTTTTCTTAG) is classified Likely pathogenic in BBS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-22). Associated with BBS2-related disorder.

What condition is associated with BBS2 p.Ala122fs (c.365_369delinsTCCTTTTACTTTTCTTAG)?

BBS2 p.Ala122fs (c.365_369delinsTCCTTTTACTTTTCTTAG) is associated with BBS2-related disorder (ClinVar).

BBS2 p.Ala122fs

c.365_369delinsTCCTTTTACTTTTCTTAG · VCV3348187

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

BBS2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP 0.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BBS2
Protein: p.Ala122fs
Coding: c.365_369delinsTCCTTTTACTTTTCTTAG
MANE Select: NM_031885
Type: Indel
Location: chr16:56511261 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49
Residue 122: a UniProt-annotated variant site (in)

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

Disease context

BBS2-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BBS2 p.Ala122= Likely benign ★★ same residue
BBS2 p.Ala122Gly Uncertain significance ★ ⚠ same residue
BBS2 p.Ala122Val Uncertain significance ★ ⚠ same residue
BBS2 c.804+1_804+14del Likely pathogenic ★★ same condition
BBS2 c.941-1G>T Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Arg216Pro Likely pathogenic ★★ same condition
BBS2 p.Arg234Ter Pathogenic ★★ same condition
BBS2 p.Arg275Ter 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-ala122fs (accessed [today's date]).

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