Is BBS7 p.Leu656fs (c.1967_1968delinsC) pathogenic?

BBS7 p.Leu656fs (c.19671968delinsC) is classified Pathogenic/Likely pathogenic in BBS7 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-21). Absent from gnomAD; Associated with BBS7-related disorder.

What condition is associated with BBS7 p.Leu656fs (c.1967_1968delinsC)?

BBS7 p.Leu656fs (c.1967_1968delinsC) is associated with BBS7-related disorder, optic atrophy, Bardet-Biedl syndrome 7 (ClinVar).

How common is BBS7 p.Leu656fs (c.1967_1968delinsC) in the general population?

BBS7 p.Leu656fs (c.1967_1968delinsC) is absent from gnomAD (gnomAD).

BBS7 p.Leu656fs

c.1967_1968delinsC · rs672601379 · VCV162088

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

BBS7-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	escapes	premature termination codon within the last 50 nt of the penultimate exon (18 of 19, 46 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.5	GERP -3.7

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: BBS7
Protein: p.Leu656fs
Coding: c.1967_1968delinsC
MANE Select: NM_176824
dbSNP: rs672601379
Type: Indel
Location: chr4:121828192 (GRCh38)
Gene constraint: LOEUF 0.701 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.99

Full BBS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BBS7-related disorder

Also linked: optic atrophy Bardet-Biedl syndrome 7 Bardet-Biedl syndrome

Similar variants

BBS7 p.Leu656= Likely benign ★ same residue
BBS7 p.Ser571Ter Pathogenic ★★ same condition
BBS7 p.Ser556_Thr557delinsArgSer Pathogenic ★ same condition
BBS7 p.Lys662fs Conflicting classifications of pathogenicity ★ same condition
BBS7 c.1890+15_1890+16delinsTA Likely benign ★ same condition
BBS7 c.1305+2T>A Likely pathogenic ★★ same condition
BBS7 c.1306-1_1308del Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.1371+1G>A 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/bbs7-p-leu656fs (accessed [today's date]).

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