Is CKAP2L p.Met1fs (c.2_3insA) pathogenic?

CKAP2L p.Met1fs (c.23insA) is classified Likely pathogenic in CKAP2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). Very rare (popmax 0.000932%, nfe).

How common is CKAP2L p.Met1fs (c.2_3insA) in the general population?

CKAP2L p.Met1fs (c.2_3insA) is very rare (popmax 0.000932%, nfe) (gnomAD).

CKAP2L p.Met1fs

c.2_3insA · VCV3337767

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

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 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 2.3, phastCons 1
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,020 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,614,056 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: CKAP2L
Protein: p.Met1fs
Coding: c.2_3insA
MANE Select: NM_152515
Type: Insertion
Location: chr2:112764596 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68

Full CKAP2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP2L p.Met1Thr Pathogenic same residue
CKAP2L p.Gly27fs 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/ckap2l-p-met1fs (accessed [today's date]).

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