Is CPLANE1 p.Glu142Lys (c.424G>A) pathogenic?

CPLANE1 p.Glu142Lys (c.424G>A) is classified Pathogenic/Likely pathogenic in CPLANE1 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-06). AlphaMissense: likely pathogenic (0.5707); Ultra-rare (popmax 0.0328%, nfe); Associated with C5ORF42 & CPLANE1-related disorders.

What condition is associated with CPLANE1 p.Glu142Lys (c.424G>A)?

CPLANE1 p.Glu142Lys (c.424G>A) is associated with C5ORF42 & CPLANE1-related disorders, orofaciodigital syndrome type 6, Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Glu142Lys (c.424G>A) in the general population?

CPLANE1 p.Glu142Lys (c.424G>A) is ultra-rare (popmax 0.0328%, nfe) (gnomAD).

What do computational predictors say about CPLANE1 p.Glu142Lys (c.424G>A)?

AlphaMissense predicts likely pathogenic (score 0.5707) — an in-silico prediction, not a clinical call.

CPLANE1 p.Glu142Lys

c.424G>A · rs756856188 · VCV217592

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely pathogenic

0.5707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0328%, nfe)

Conditions

C5ORF42 & CPLANE1-related disorders

Computational evidence

Protein change
AlphaMissense	0.5707	likely pathogenic ✓ concordant with ClinVar
REVEL	0.312	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	26.7	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 0.0328% European (non-Finnish) · 376/1,146,988 alleles

Filtering AF 0.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0289%

Overall 0.0258% 400/1,551,530 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0349%	2,865
European (non-Finnish)grpmax	0.0328%	3,051
African / African-American	0.00411%	24,321

Remaining individuals 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: CPLANE1
Protein: p.Glu142Lys
Coding: c.424G>A
MANE Select: NM_001384732
dbSNP: rs756856188
Type: single nucleotide variant
Location: chr5:37244521 (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

C5ORF42 & CPLANE1-related disorders

Also linked: orofaciodigital syndrome type 6 Joubert syndrome 17 Joubert syndrome and related disorders nephronophthisis

Similar variants

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.2920+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-glu142lys (accessed [today's date]).

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