Is CKAP2L p.Pro587Arg (c.1760C>G) pathogenic?

CKAP2L p.Pro587Arg (c.1760C>G) is classified Uncertain significance in CKAP2L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely pathogenic (0.8472); Very rare (popmax 0.00402%, afr); Associated with Inborn genetic diseases.

What condition is associated with CKAP2L p.Pro587Arg (c.1760C>G)?

CKAP2L p.Pro587Arg (c.1760C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CKAP2L p.Pro587Arg (c.1760C>G) in the general population?

CKAP2L p.Pro587Arg (c.1760C>G) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about CKAP2L p.Pro587Arg (c.1760C>G)?

AlphaMissense predicts likely pathogenic (score 0.8472) — an in-silico prediction, not a clinical call.

CKAP2L p.Pro587Arg

c.1760C>G · VCV4003178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8472 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8472	likely pathogenic · top 4% in CKAP2L
REVEL	0.645	pathogenic-leaning
SaProt	LLR -13.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00402% African / African-American · 3/74,540 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.00197% 3/152,172 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.Pro587Arg
Coding: c.1760C>G
MANE Select: NM_152515
Type: single nucleotide variant
Location: chr2:112742768 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CKAP2L p.Arg206Gly Uncertain significance ★★ ⚠ same condition
CKAP2L p.Arg284Trp Uncertain significance ★★ ⚠ same condition
CKAP2L p.Arg688Gln Uncertain significance ★★ ⚠ same condition
CKAP2L p.Gln428Arg Uncertain significance ★★ ⚠ same condition
CKAP2L p.Ile283Leu Uncertain significance ★★ ⚠ same condition
CKAP2L p.Lys421Arg Uncertain significance ★★ ⚠ same condition
CKAP2L p.Lys480Glu Uncertain significance ★★ ⚠ same condition
CKAP2L p.Pro670Ser Uncertain significance ★★ ⚠ 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/ckap2l-p-pro587arg (accessed [today's date]).

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