Is BBS5 p.Val71Ile (c.211G>A) pathogenic?

BBS5 p.Val71Ile (c.211G>A) is classified Conflicting classifications of pathogenicity in BBS5 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-01-23). AlphaMissense: likely benign (0.0643); Very rare (popmax 0.0069%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BBS5 p.Val71Ile (c.211G>A)?

BBS5 p.Val71Ile (c.211G>A) is associated with Inborn genetic diseases, Bardet-Biedl syndrome 5, Bardet-Biedl syndrome (ClinVar).

How common is BBS5 p.Val71Ile (c.211G>A) in the general population?

BBS5 p.Val71Ile (c.211G>A) is very rare (popmax 0.0069%, nfe) (gnomAD).

What do computational predictors say about BBS5 p.Val71Ile (c.211G>A)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

BBS5 p.Val71Ile

c.211G>A · rs1397496181 · VCV1042319

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0069%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR 0.23	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 3.9	GERP -2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.023 · regional, not allelic
Overall
CADD	12.52	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 0.0069% European (non-Finnish) · 81/1,174,624 alleles

Filtering AF 0.00565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00517%

Overall 0.00504% 81/1,606,364 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: BBS5
Protein: p.Val71Ile
Coding: c.211G>A
MANE Select: NM_152384
dbSNP: rs1397496181
Type: single nucleotide variant
Location: chr2:169487808 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 1 PDB

Full BBS5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 5 Bardet-Biedl syndrome

Similar variants

BBS5 c.143-1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-2A>G Likely pathogenic ★★ same condition
BBS5 c.522+3A>G Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.681+1G>T Pathogenic/Likely pathogenic ★★ same condition
BBS5 p.Arg138Cys Likely pathogenic ★★ same condition
BBS5 p.Arg138His Pathogenic/Likely pathogenic ★★ same condition
BBS5 p.Arg89Ter 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/bbs5-p-val71ile (accessed [today's date]).

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