Is BBS7 p.Arg160His (c.479G>A) pathogenic?

BBS7 p.Arg160His (c.479G>A) is classified Uncertain significance in BBS7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-29). AlphaMissense: likely benign (0.0642); Ultra-rare (popmax 0.0147%, afr); Associated with Bardet-Biedl syndrome 7.

What condition is associated with BBS7 p.Arg160His (c.479G>A)?

BBS7 p.Arg160His (c.479G>A) is associated with Bardet-Biedl syndrome 7, Bardet-Biedl syndrome (ClinVar).

How common is BBS7 p.Arg160His (c.479G>A) in the general population?

BBS7 p.Arg160His (c.479G>A) is ultra-rare (popmax 0.0147%, afr) (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.Arg160His (c.479G>A)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

BBS7 p.Arg160His

c.479G>A · rs138270119 · VCV962347

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome 7

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -7.03	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 -0.56	GERP -3.1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	14.03	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 0.0147% African / African-American · 11/74,840 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000744% 12/1,613,670 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,804
European (non-Finnish)	8.48e-05%	1,179,892

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.Arg160His
Coding: c.479G>A
MANE Select: NM_176824
dbSNP: rs138270119
Type: single nucleotide variant
Location: chr4:121859041 (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

Also linked: Bardet-Biedl syndrome

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.Arg160Cys Uncertain significance ★★ ⚠ 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
BBS7 c.529-2A>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-arg160his (accessed [today's date]).

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