Is CPLANE1 p.Arg978Gln (c.2933G>A) pathogenic?

CPLANE1 p.Arg978Gln (c.2933G>A) is classified Uncertain significance in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-07). AlphaMissense: likely benign (0.325); Very rare (popmax 0.00489%, eas); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Arg978Gln (c.2933G>A)?

CPLANE1 p.Arg978Gln (c.2933G>A) is associated with Joubert syndrome 17, orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Arg978Gln (c.2933G>A) in the general population?

CPLANE1 p.Arg978Gln (c.2933G>A) is very rare (popmax 0.00489%, eas) (gnomAD).

What do computational predictors say about CPLANE1 p.Arg978Gln (c.2933G>A)?

AlphaMissense predicts likely benign (score 0.325) — an in-silico prediction, not a clinical call.

CPLANE1 p.Arg978Gln

c.2933G>A · rs992985282 · VCV907933

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.325 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00489%, eas)

Conditions

Joubert syndrome 17

Computational evidence

Protein change
AlphaMissense	0.325	likely benign
REVEL	0.428	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	28.2	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 0.00489% East Asian · 2/40,918 alleles

Filtering AF 0.00081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000303%

Overall 0.000903% 14/1,549,660 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00489%	20,459
Admixed American	0.00392%	25,490
South Asian	0.00238%	41,997
African / African-American	0.00137%	72,976
European (non-Finnish)	0.000611%	163,615

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.Arg978Gln
Coding: c.2933G>A
MANE Select: NM_001384732
dbSNP: rs992985282
Type: single nucleotide variant
Location: chr5:37206413 (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

Also linked: orofaciodigital syndrome type 6

Similar variants

CPLANE1 p.Arg978Ter Pathogenic ★★ same residue
CPLANE1 p.Arg978= Likely benign ★ 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

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-arg978gln (accessed [today's date]).

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