Is CPLANE1 p.Arg2467fs (c.7399del) pathogenic?

CPLANE1 p.Arg2467fs (c.7399del) is classified Pathogenic in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). Very rare (popmax 0.00114%, sas).

How common is CPLANE1 p.Arg2467fs (c.7399del) in the general population?

CPLANE1 p.Arg2467fs (c.7399del) is very rare (popmax 0.00114%, sas) (gnomAD).

CPLANE1 p.Arg2467fs

c.7399del · rs779025515 · VCV1452683

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

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 35 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00114% South Asian · 1/87,982 alleles

Overall 0.000138% 2/1,451,096 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,170
South Asiangrpmax	0.00114%	87,982

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.Arg2467fs
Coding: c.7399del
MANE Select: NM_001384732
dbSNP: rs779025515
Type: Deletion
Location: chr5:37167048 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2467: a UniProt-annotated variant site (in ofd6; likely pathogenic); the 'disordered' region

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

Similar variants

CPLANE1 p.Asn1182fs Pathogenic ★★ same type
CPLANE1 p.Gln1399fs Pathogenic/Likely pathogenic ★★ same type
CPLANE1 p.Gly2717fs Pathogenic ★★ same type
CPLANE1 p.His961fs Pathogenic/Likely pathogenic ★★ same type
CPLANE1 p.Ile165fs Pathogenic ★★ same type
CPLANE1 p.Ile1889_Asp1890insTer Likely pathogenic ★★ same type
CPLANE1 p.Leu465fs Pathogenic/Likely pathogenic ★★ same type
CPLANE1 p.Leu808fs Pathogenic/Likely pathogenic ★★ same type

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-arg2467fs (accessed [today's date]).

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