Is CKAP4 p.Pro367Arg (c.1100C>G) pathogenic?

CKAP4 p.Pro367Arg (c.1100C>G) is classified Uncertain significance in CKAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: ambiguous (0.4222); Very rare (popmax 0.000254%, nfe).

How common is CKAP4 p.Pro367Arg (c.1100C>G) in the general population?

CKAP4 p.Pro367Arg (c.1100C>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CKAP4 p.Pro367Arg (c.1100C>G)?

AlphaMissense predicts ambiguous (score 0.4222) — an in-silico prediction, not a clinical call.

CKAP4 p.Pro367Arg

c.1100C>G · VCV4003189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4222	ambiguous
REVEL	0.442	indeterminate
SaProt	LLR -11.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,007 bp · p 0.25 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,986 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,786 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: CKAP4
Protein: p.Pro367Arg
Coding: c.1100C>G
MANE Select: NM_006825
Type: single nucleotide variant
Location: chr12:106239733 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.61

Full CKAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP4 p.Pro367Leu Uncertain significance ★ ⚠ same residue
CKAP4 p.His444= Benign ★★ same type
CKAP4 p.Leu580Val Benign ★★ same type
CKAP4 p.Thr236= Benign ★★ same type
CKAP4 p.Tyr483= Likely benign ★★ same type
CKAP4 p.Ala167Gly Uncertain significance ★ ⚠ same type
CKAP4 p.Ala23Gly Uncertain significance ★ ⚠ same type
CKAP4 p.Ala449Thr Uncertain significance ★ ⚠ 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/ckap4-p-pro367arg (accessed [today's date]).

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