Is BBS4 p.Ile31Val (c.91A>G) pathogenic?

BBS4 p.Ile31Val (c.91A>G) is classified Benign in BBS4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2009-10-13). AlphaMissense: likely benign (0.08); Very rare (popmax 0.00223%, eas); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS4 p.Ile31Val (c.91A>G)?

BBS4 p.Ile31Val (c.91A>G) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS4 p.Ile31Val (c.91A>G) in the general population?

BBS4 p.Ile31Val (c.91A>G) is very rare (popmax 0.00223%, 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 BBS4 p.Ile31Val (c.91A>G)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

BBS4 p.Ile31Val

c.91A>G · rs113994182 · VCV21742

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.68	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 1.3	GERP 1.2, phastCons 0.068
Regional constraint	o/e 1.09	unconstrained · MANE · 51 kb · p 0.035 · regional, not allelic
Overall
CADD	14.98	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 0.00223% East Asian · 1/44,856 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00089% 13/1,460,988 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00782%	12,782
East Asiangrpmax	0.00223%	44,856
South Asian	0.0011%	91,064
European (non-Finnish)	0.000509%	196,556

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BBS4
Protein: p.Ile31Val
Coding: c.91A>G
MANE Select: NM_033028
dbSNP: rs113994182
Type: single nucleotide variant
Location: chr15:72709714 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 1 PDB
Residue 31: the 'required for localization to centrosomes' region

Full BBS4 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

BBS4 c.1106+2T>A Pathogenic/Likely pathogenic ★★ same condition
BBS4 c.1248+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS4 c.1248+1G>T Pathogenic ★★ same condition
BBS4 c.1248+2T>C Pathogenic/Likely pathogenic ★★ same condition
BBS4 c.1249-2A>C Likely pathogenic ★★ same condition
BBS4 c.157-2A>G Pathogenic ★★ same condition
BBS4 c.157-3C>G Pathogenic ★★ same condition
BBS4 c.220+1G>C 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/bbs4-p-ile31val (accessed [today's date]).

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