Is B9D1 p.Val72= (c.216C>G) pathogenic?

B9D1 p.Val72= (c.216C>G) is classified Likely benign in B9D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). Very rare (popmax 0.000254%, nfe); Associated with Joubert syndrome.

What condition is associated with B9D1 p.Val72= (c.216C>G)?

B9D1 p.Val72= (c.216C>G) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D1 p.Val72= (c.216C>G) in the general population?

B9D1 p.Val72= (c.216C>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

B9D1 p.Val72=

c.216C>G · rs142357986 · VCV2925767

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.74, phastCons 1
Overall
CADD	8.363	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,976 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,898 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: B9D1
Protein: p.Val72=
Coding: c.216C>G
MANE Select: NM_015681
dbSNP: rs142357986
Type: single nucleotide variant
Location: chr17:19357868 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 72: the c2 b9-type domain

Full B9D1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Meckel syndrome

Similar variants

B9D1 c.341+2T>C Pathogenic/Likely pathogenic ★★ same condition
B9D1 p.Arg114Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
B9D1 p.Arg156Trp Pathogenic/Likely pathogenic ★★ same condition
B9D1 c.404+5G>C Uncertain significance ★★ same condition
B9D1 p.Ala44Val Uncertain significance ★★ ⚠ same condition
B9D1 p.Arg101Gln Uncertain significance ★★ same condition
B9D1 p.Arg140Gln Uncertain significance ★★ ⚠ same condition
B9D1 p.Arg162His Uncertain significance ★★ ⚠ 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/b9d1-p-val72 (accessed [today's date]).

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