Is CKAP5 p.Pro1958Arg (c.5873C>G) pathogenic?

CKAP5 p.Pro1958Arg (c.5873C>G) is classified Uncertain significance in CKAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.2); Very rare (popmax 0.00322%, nfe).

How common is CKAP5 p.Pro1958Arg (c.5873C>G) in the general population?

CKAP5 p.Pro1958Arg (c.5873C>G) is very rare (popmax 0.00322%, nfe) (gnomAD).

What do computational predictors say about CKAP5 p.Pro1958Arg (c.5873C>G)?

AlphaMissense predicts likely benign (score 0.2) — an in-silico prediction, not a clinical call.

CKAP5 p.Pro1958Arg

c.5873C>G · rs147465744 · VCV2601902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 19 kb · p 9.2e-20 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00322% European (non-Finnish) · 38/1,180,032 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00254% 41/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,053
Finnishnot grpmax-eligible	0.00312%	32,014
African / African-American	0.00134%	74,900

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: CKAP5
Protein: p.Pro1958Arg
Coding: c.5873C>G
MANE Select: NM_001008938
dbSNP: rs147465744
Type: single nucleotide variant
Location: chr11:46744249 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 3 PDB
Residue 1958: the 'disordered' region

Full CKAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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CKAP5 p.Ala124Thr Uncertain significance ★ ⚠ same type
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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/ckap5-p-pro1958arg (accessed [today's date]).

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