Is CPLANE1 p.Val339fs (c.1015del) pathogenic?

CPLANE1 p.Val339fs (c.1015del) is classified Pathogenic/Likely pathogenic in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-18). Very rare (popmax 0.00245%, eas); Associated with CPLANE1-related disorders.

What condition is associated with CPLANE1 p.Val339fs (c.1015del)?

CPLANE1 p.Val339fs (c.1015del) is associated with CPLANE1-related disorders (ClinVar).

How common is CPLANE1 p.Val339fs (c.1015del) in the general population?

CPLANE1 p.Val339fs (c.1015del) is very rare (popmax 0.00245%, eas) (gnomAD).

CPLANE1 p.Val339fs

c.1015del · VCV4713374

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00245%, eas)

Conditions

CPLANE1-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00245% East Asian · 1/40,888 alleles

Overall 0.000143% 2/1,398,956 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00245%	40,888
Remaining individualsnot grpmax-eligible	0.00166%	60,202

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.Val339fs
Coding: c.1015del
MANE Select: NM_001384732
Type: Deletion
Location: chr5:37230973 (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

CPLANE1-related disorders

Similar variants

CPLANE1 p.Gly2717fs Pathogenic ★★ same condition
CPLANE1 p.His961fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Ile165fs Pathogenic ★★ same condition
CPLANE1 p.Ile1889_Asp1890insTer Likely pathogenic ★★ same condition
CPLANE1 p.Leu808fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Met594fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Ser2554fs Pathogenic ★★ same condition
CPLANE1 p.Val339Ile Uncertain significance ★★ ⚠ same residue

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-val339fs (accessed [today's date]).

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