Is BBS7 p.His351Arg (c.1052A>G) pathogenic?

BBS7 p.His351Arg (c.1052A>G) is classified Uncertain significance in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-30). AlphaMissense: likely benign (0.0812); Ultra-rare (popmax 0.0425%, eas); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS7 p.His351Arg (c.1052A>G)?

BBS7 p.His351Arg (c.1052A>G) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS7 p.His351Arg (c.1052A>G) in the general population?

BBS7 p.His351Arg (c.1052A>G) is ultra-rare (popmax 0.0425%, eas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

What do computational predictors say about BBS7 p.His351Arg (c.1052A>G)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

BBS7 p.His351Arg

c.1052A>G · rs940315256 · VCV1957351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0425%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	19.69	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0425% East Asian · 19/44,706 alleles

Filtering AF 0.0278% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00137% 20/1,460,402 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0425%	2,353
Remaining individualsnot grpmax-eligible	0.0016%	62,446

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.His351Arg
Coding: c.1052A>G
MANE Select: NM_176824
dbSNP: rs940315256
Type: single nucleotide variant
Location: chr4:121845682 (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 — 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.His351Leu Uncertain significance ★ ⚠ same residue
BBS7 p.His351= Likely benign ★ same residue
BBS7 c.1305+2T>A Likely pathogenic ★★ same condition
BBS7 c.1371+1G>A Likely pathogenic ★★ same condition
BBS7 c.1512-1G>A Likely pathogenic ★★ same condition
BBS7 c.1677-2A>G Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.1891-2A>C Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.342-2A>G 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-his351arg (accessed [today's date]).

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