Is B9D2 p.Val39Met (c.115G>A) pathogenic?

B9D2 p.Val39Met (c.115G>A) is classified Uncertain significance in B9D2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-06). AlphaMissense: likely benign (0.0895); Very rare (popmax 0.00891%, eas); Associated with Joubert syndrome.

What condition is associated with B9D2 p.Val39Met (c.115G>A)?

B9D2 p.Val39Met (c.115G>A) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is B9D2 p.Val39Met (c.115G>A) in the general population?

B9D2 p.Val39Met (c.115G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about B9D2 p.Val39Met (c.115G>A)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

B9D2 p.Val39Met

c.115G>A · rs761158280 · VCV1363298

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -7.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.3
Regional constraint	o/e 0.90	unconstrained · MANE · 8,816 bp · p 0.14 · regional, not allelic
Overall
CADD	11.53	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00103% 15/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,032
European (non-Finnish)	0.000339%	295,003

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.Val39Met
Coding: c.115G>A
MANE Select: NM_030578
dbSNP: rs761158280
Type: single nucleotide variant
Location: chr19:41357996 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79
Residue 39: 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 c.215-16C>G Benign ★★ 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-val39met (accessed [today's date]).

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