Is BBS7 p.Ser581fs (c.1741del) pathogenic?

BBS7 p.Ser581fs (c.1741del) is classified Likely pathogenic in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Very rare (popmax 0.0011%, sas); Associated with BBS7-related disorder.

What condition is associated with BBS7 p.Ser581fs (c.1741del)?

BBS7 p.Ser581fs (c.1741del) is associated with BBS7-related disorder (ClinVar).

How common is BBS7 p.Ser581fs (c.1741del) in the general population?

BBS7 p.Ser581fs (c.1741del) is very rare (popmax 0.0011%, sas) (gnomAD).

BBS7 p.Ser581fs

c.1741del · VCV4968374

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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	predicted	premature termination codon in exon 16 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,812 alleles

Overall 0.000124% 2/1,610,338 alleles · very rare exomes 1/1,458,244 · genomes 1/152,094 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,812
European (non-Finnish)	8.49e-05%	1,177,372

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BBS7
Protein: p.Ser581fs
Coding: c.1741del
MANE Select: NM_176824
Type: Deletion
Location: chr4:121828664 (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

Similar variants

BBS7 p.Gln657fs Pathogenic ★★ same condition
BBS7 p.Gly329del Uncertain significance same condition
BBS7 c.1038-6del Likely benign same condition
BBS7 c.529-2A>G Pathogenic/Likely pathogenic ★★ same condition
BBS7 p.Arg238fs Pathogenic ★★ same condition
BBS7 p.His323Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
BBS7 p.Leu656fs Pathogenic/Likely pathogenic ★★ same condition
BBS7 p.Thr191fs 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/bbs7-p-ser581fs (accessed [today's date]).

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