Is CKAP2 p.Pro173Arg (c.518C>G) pathogenic?

CKAP2 p.Pro173Arg (c.518C>G) is classified Uncertain significance in CKAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.141); Absent from gnomAD v4.1.

How common is CKAP2 p.Pro173Arg (c.518C>G) in the general population?

CKAP2 p.Pro173Arg (c.518C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CKAP2 p.Pro173Arg (c.518C>G)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

CKAP2 p.Pro173Arg

c.518C>G · VCV4229210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.51	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 0.95	GERP 0.95, phastCons 0.94
Regional constraint	o/e 1.06	unconstrained · MANE · 6,978 bp · p 0.17 · regional, not allelic
Overall
CADD	10.85	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P174R vs ClinVar P173R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CKAP2
Protein: p.Pro173Arg
Coding: c.518C>G
MANE Select: NM_018204
Type: single nucleotide variant
Location: chr13:52461344 (GRCh38)
Gene constraint: LOEUF 0.983 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.29
Residue 173: the 'disordered' region

Full CKAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP2 p.Pro173Ser Uncertain significance ★ ⚠ same residue
CKAP2 p.Arg628Gln Uncertain significance ★★ ⚠ same type
CKAP2 p.Asn386Asp Benign ★★ same type
CKAP2 p.Thr312= Benign ★★ same type
CKAP2 p.Ala214Ser Uncertain significance ★ ⚠ same type
CKAP2 p.Ala326Thr Uncertain significance ★ ⚠ same type
CKAP2 p.Ala347Ser Uncertain significance ★ ⚠ same type
CKAP2 p.Ala350Thr 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/ckap2-p-pro173arg (accessed [today's date]).

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