Is B9D1 p.Pro79= (c.237C>G) pathogenic?

B9D1 p.Pro79= (c.237C>G) is classified Benign/Likely benign in B9D1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Rare (popmax 0.935%, afr); Associated with Joubert syndrome.

What condition is associated with B9D1 p.Pro79= (c.237C>G)?

B9D1 p.Pro79= (c.237C>G) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D1 p.Pro79= (c.237C>G) in the general population?

B9D1 p.Pro79= (c.237C>G) is rare (popmax 0.935%, afr) (gnomAD).

B9D1 p.Pro79=

c.237C>G · rs149051059 · VCV260672

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.935%, 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 -0.29	GERP -2.9, phastCons 0.009
Overall
CADD	3.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.935% African / African-American · 702/75,042 alleles

Filtering AF 0.878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.855%

Overall 0.0477% 770/1,613,700 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.935%	107
Admixed American	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.048%	2,083
Middle Eastern	0.017%	5,884
South Asian	0.0011%	91,046
European (non-Finnish)	0.000593%	168,540

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.Pro79=
Coding: c.237C>G
MANE Select: NM_015681
dbSNP: rs149051059
Type: single nucleotide variant
Location: chr17:19357847 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 79: 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 p.Pro79Leu Uncertain significance ★★ ⚠ same residue
B9D1 p.Pro79Ala Uncertain significance ★ same residue
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

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-pro79 (accessed [today's date]).

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