Is B9D2 p.Ile61= (c.183C>T) pathogenic?

B9D2 p.Ile61= (c.183C>T) is classified Benign/Likely benign in B9D2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-24). Rare (popmax 0.501%, afr); Associated with Joubert syndrome.

What condition is associated with B9D2 p.Ile61= (c.183C>T)?

B9D2 p.Ile61= (c.183C>T) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D2 p.Ile61= (c.183C>T) in the general population?

B9D2 p.Ile61= (c.183C>T) is rare (popmax 0.501%, afr) (gnomAD).

B9D2 p.Ile61=

c.183C>T · rs140901774 · VCV695821

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.501%, afr)

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 -1.7	GERP -3.3
Overall
CADD	6.586	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.501% African / African-American · 376/75,042 alleles

Filtering AF 0.459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.443%

Overall 0.0278% 448/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.501%	200
Admixed American	0.0433%	2,308
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Middle Eastern	0.0165%	6,050
East Asian	0.00446%	22,441
European (non-Finnish)	0.00178%	56,191
South Asian	0.0011%	91,074

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: B9D2
Protein: p.Ile61=
Coding: c.183C>T
MANE Select: NM_030578
dbSNP: rs140901774
Type: single nucleotide variant
Location: chr19:41357928 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 61: the c2 b9-type domain

Full B9D2 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

B9D2 p.Gly155Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Pro74Ser Pathogenic/Likely pathogenic ★★ same condition
B9D2 p.Arg88Cys Uncertain significance ★★ ⚠ same condition
B9D2 p.Gln50His Uncertain significance ★★ ⚠ same condition
B9D2 p.Gly162Cys Uncertain significance ★★ ⚠ same condition
B9D2 p.Pro103Ser Uncertain significance ★★ ⚠ same condition
B9D2 p.Thr44Met Uncertain significance ★★ ⚠ same condition
B9D2 p.Val39Met 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/b9d2-p-ile61 (accessed [today's date]).

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