Is BBS7 p.His323Arg (c.968A>G) pathogenic?

BBS7 p.His323Arg (c.968A>G) is classified Pathogenic/Likely pathogenic in BBS7 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.0647); Very rare (popmax 0.00763%, nfe); Associated with BBS7-related disorder.

What condition is associated with BBS7 p.His323Arg (c.968A>G)?

BBS7 p.His323Arg (c.968A>G) is associated with BBS7-related disorder, Bardet-Biedl syndrome 7, Bardet-Biedl syndrome (ClinVar).

How common is BBS7 p.His323Arg (c.968A>G) in the general population?

BBS7 p.His323Arg (c.968A>G) is very rare (popmax 0.00763%, nfe) (gnomAD).

What do computational predictors say about BBS7 p.His323Arg (c.968A>G)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

BBS7 p.His323Arg

c.968A>G · rs119466001 · VCV3015

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00763%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BBS7-related disorder

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign ⚠ discordant with ClinVar
REVEL	0.473	indeterminate
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
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	18.95	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00763% European (non-Finnish) · 90/1,179,764 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.00583% 94/1,613,656 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,108
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00267%	37,467

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.His323Arg
Coding: c.968A>G
MANE Select: NM_176824
dbSNP: rs119466001
Type: single nucleotide variant
Location: chr4:121847473 (GRCh38)
Gene constraint: LOEUF 0.701 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.99
Residue 323: a UniProt-annotated variant site (in bbs7)

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

Disease context

BBS7-related disorder

Also linked: Bardet-Biedl syndrome 7 Bardet-Biedl syndrome inherited retinal dystrophy

Similar variants

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
BBS7 c.849+1G>C 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-his323arg (accessed [today's date]).

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