Is CPLANE1 p.Ser2554fs (c.7662_7666del) pathogenic?

CPLANE1 p.Ser2554fs (c.76627666del) is classified Pathogenic in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-27). Very rare (popmax 0.005%, amr); Associated with CPLANE1-related disorders.

What condition is associated with CPLANE1 p.Ser2554fs (c.7662_7666del)?

CPLANE1 p.Ser2554fs (c.7662_7666del) is associated with CPLANE1-related disorders (ClinVar).

How common is CPLANE1 p.Ser2554fs (c.7662_7666del) in the general population?

CPLANE1 p.Ser2554fs (c.7662_7666del) is very rare (popmax 0.005%, amr) (gnomAD).

CPLANE1 p.Ser2554fs

c.7662_7666del · rs756416171 · VCV2714930

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 38 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	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 0.005% Admixed American · 3/59,990 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000206% 3/1,459,004 alleles · very rare

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.Ser2554fs
Coding: c.7662_7666del
MANE Select: NM_001384732
dbSNP: rs756416171
Type: Deletion
Location: chr5:37162489 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2554: a UniProt-annotated variant site (in ofd6; likely pathogenic)

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.Val339fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Cys1321fs 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-ser2554fs (accessed [today's date]).

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