Is BBS1 p.Ser375fs (c.1123dup) pathogenic?

BBS1 p.Ser375fs (c.1123dup) is classified Pathogenic in BBS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-01). Absent from gnomAD.

How common is BBS1 p.Ser375fs (c.1123dup) in the general population?

BBS1 p.Ser375fs (c.1123dup) is absent from gnomAD (gnomAD).

BBS1 p.Ser375fs

c.1123dup · rs1856478896 · VCV871876

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP 0.057, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BBS1
Protein: p.Ser375fs
Coding: c.1123dup
MANE Select: NM_024649
dbSNP: rs1856478896
Type: Duplication
Location: chr11:66526134 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 1 PDB

Full BBS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BBS1 p.Ser375Arg Likely pathogenic ★ same residue
BBS1 p.Ser375= Likely benign ★ same residue
BBS1 p.Ala107fs Pathogenic/Likely pathogenic ★★ same type
BBS1 p.Arg429fs Pathogenic/Likely pathogenic ★★ same type
BBS1 p.Leu468fs Pathogenic/Likely pathogenic ★★ same type
BBS1 p.Leu54fs Pathogenic/Likely pathogenic ★★ same type
BBS1 p.Ser7fs Pathogenic/Likely pathogenic ★★ same type
BBS1 c.1473+16_1473+18dup Likely benign ★★ 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/bbs1-p-ser375fs (accessed [today's date]).

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