Is B9D1 p.Ala63= (c.189A>G) pathogenic?

B9D1 p.Ala63= (c.189A>G) is classified Likely benign in B9D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). Very rare (popmax 0.00659%, sas); Associated with Joubert syndrome.

What condition is associated with B9D1 p.Ala63= (c.189A>G)?

B9D1 p.Ala63= (c.189A>G) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D1 p.Ala63= (c.189A>G) in the general population?

B9D1 p.Ala63= (c.189A>G) is very rare (popmax 0.00659%, sas) (gnomAD).

B9D1 p.Ala63=

c.189A>G · rs779880608 · VCV2162104

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

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 -4.7	GERP -2.9
Overall
CADD	2.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,082 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000372% 6/1,614,166 alleles · very rare exomes 6/1,461,864 · genomes 0/152,302 · joint denominator

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.Ala63=
Coding: c.189A>G
MANE Select: NM_015681
dbSNP: rs779880608
Type: single nucleotide variant
Location: chr17:19357895 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 63: 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-ala63 (accessed [today's date]).

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