Is CPLANE1 p.Val32Ile (c.94G>A) pathogenic?

CPLANE1 p.Val32Ile (c.94G>A) is classified Benign in CPLANE1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.086); Common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Val32Ile (c.94G>A)?

CPLANE1 p.Val32Ile (c.94G>A) is associated with Joubert syndrome 17 (ClinVar).

What do computational predictors say about CPLANE1 p.Val32Ile (c.94G>A)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

CPLANE1 p.Val32Ile

Q: How common is CPLANE1 p.Val32Ile (c.94G>A) in the general population?

CPLANE1 p.Val32Ile (c.94G>A) is common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.94G>A · rs73750959 · VCV158062

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.117	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.1% African / African-American · 7,146/71,056 alleles

Filtering AF 9.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.78%

Overall 0.529% 7,995/1,510,238 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.1%	10
Admixed American	0.819%	122
Remaining individualsnot grpmax-eligible	0.687%	146
Middle Eastern	0.202%	495
South Asian	0.031%	3,230
European (non-Finnish)	0.00601%	16,652
East Asian	0.0025%	40,000

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: CPLANE1
Protein: p.Val32Ile
Coding: c.94G>A
MANE Select: NM_001384732
dbSNP: rs73750959
Type: single nucleotide variant
Location: chr5:37245833 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

Full CPLANE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPLANE1 p.Val32Phe Uncertain significance ★ same residue
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2291+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2292-1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2500+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.3290-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.3673-1G>C Pathogenic/Likely pathogenic ★★ 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/cplane1-p-val32ile (accessed [today's date]).

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