Is B9D2 p.Phe65= (c.195C>T) pathogenic?

B9D2 p.Phe65= (c.195C>T) is classified Benign/Likely benign in B9D2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). Rare (popmax 0.323%, nfe); Associated with Joubert syndrome.

What condition is associated with B9D2 p.Phe65= (c.195C>T)?

B9D2 p.Phe65= (c.195C>T) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D2 p.Phe65= (c.195C>T) in the general population?

B9D2 p.Phe65= (c.195C>T) is rare (popmax 0.323%, nfe) (gnomAD).

B9D2 p.Phe65=

c.195C>T · rs34088631 · VCV241603

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.323%, 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 -1.5	GERP -3.3
Overall
CADD	6.345	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.323% European (non-Finnish) · 3,809/1,180,004 alleles

Filtering AF 0.314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.311%

Overall 0.262% 4,231/1,614,138 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.877%	114
European (non-Finnish)grpmax	0.323%	310
Admixed American	0.292%	343
Remaining individualsnot grpmax-eligible	0.218%	460
Middle Eastern	0.182%	550
African / African-American	0.0666%	1,501
Finnishnot grpmax-eligible	0.0484%	2,066
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921
South Asian	0.00659%	15,181

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe65=
Coding: c.195C>T
MANE Select: NM_030578
dbSNP: rs34088631
Type: single nucleotide variant
Location: chr19:41357916 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 65: 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-phe65 (accessed [today's date]).

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