Is BBS7 p.Ser110fs (c.328del) pathogenic?

BBS7 p.Ser110fs (c.328del) is classified Likely pathogenic in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-15). Very rare (popmax 0.00401%, afr); Associated with Bardet-Biedl syndrome 7.

What condition is associated with BBS7 p.Ser110fs (c.328del)?

BBS7 p.Ser110fs (c.328del) is associated with Bardet-Biedl syndrome 7 (ClinVar).

How common is BBS7 p.Ser110fs (c.328del) in the general population?

BBS7 p.Ser110fs (c.328del) is very rare (popmax 0.00401%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

BBS7 p.Ser110fs

c.328del · rs1430683955 · VCV2680086

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 0.00401%, afr)

Conditions

Bardet-Biedl syndrome 7

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 4 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Overall
CADD	29.3	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 0.00401% African / African-American · 3/74,796 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,612,034 alleles · very rare

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.Ser110fs
Coding: c.328del
MANE Select: NM_176824
dbSNP: rs1430683955
Type: Deletion
Location: chr4:121861517 (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

Bardet-Biedl syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS7 p.Ser110Asn Uncertain significance ★★ ⚠ same residue
BBS7 c.1306-1_1308del Pathogenic/Likely pathogenic ★★ same condition
BBS7 p.Asn130fs Pathogenic ★★ same condition
BBS7 p.Asn335fs Pathogenic ★★ same condition
BBS7 p.Gln657fs Pathogenic ★★ same condition
BBS7 p.Pro25fs Pathogenic/Likely pathogenic ★★ same condition
BBS7 p.Val531_Pro532del Pathogenic/Likely pathogenic ★★ same condition
BBS7 p.Ile397fs 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-ser110fs (accessed [today's date]).

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