Is CPLANE1 p.Lys613= (c.1839A>G) pathogenic?

CPLANE1 p.Lys613= (c.1839A>G) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-21). Ultra-rare (popmax 0.0365%, sas); Associated with orofaciodigital syndrome type 6.

What condition is associated with CPLANE1 p.Lys613= (c.1839A>G)?

CPLANE1 p.Lys613= (c.1839A>G) is associated with orofaciodigital syndrome type 6, Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Lys613= (c.1839A>G) in the general population?

CPLANE1 p.Lys613= (c.1839A>G) is ultra-rare (popmax 0.0365%, sas) (gnomAD).

CPLANE1 p.Lys613=

c.1839A>G · rs533310477 · VCV385383

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0365%, sas)

Conditions

orofaciodigital syndrome type 6

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 -0.071	GERP -3.2, phastCons 0.88
Overall
CADD	3.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0365% South Asian · 30/82,142 alleles

Filtering AF 0.0262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.00356% 55/1,543,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0365%	2,738
Middle Eastern	0.0168%	5,938
Remaining individualsnot grpmax-eligible	0.00502%	19,915
European (non-Finnish)	0.00184%	54,450

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.Lys613=
Coding: c.1839A>G
MANE Select: NM_001384732
dbSNP: rs533310477
Type: single nucleotide variant
Location: chr5:37226756 (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

orofaciodigital syndrome type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 17

Similar variants

CPLANE1 p.Lys613Asn Conflicting classifications of pathogenicity ★ 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-lys613 (accessed [today's date]).

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