Is CKAP2 p.Arg629Cys (c.1885C>T) pathogenic?

CKAP2 p.Arg629Cys (c.1885C>T) is classified Uncertain significance in CKAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). AlphaMissense: likely pathogenic (0.7461); Very rare (popmax 0.00407%, nfe).

How common is CKAP2 p.Arg629Cys (c.1885C>T) in the general population?

CKAP2 p.Arg629Cys (c.1885C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

What do computational predictors say about CKAP2 p.Arg629Cys (c.1885C>T)?

AlphaMissense predicts likely pathogenic (score 0.7461) — an in-silico prediction, not a clinical call.

CKAP2 p.Arg629Cys

c.1885C>T · VCV3833614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7461	likely pathogenic · top 6% in CKAP2
REVEL	0.218	benign-leaning
SaProt	LLR -10.36	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 9,828 bp · p 0.79 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R630C vs ClinVar R629C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,180,006 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00316% 51/1,614,020 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,583
South Asian	0.0022%	45,541
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: CKAP2
Protein: p.Arg629Cys
Coding: c.1885C>T
MANE Select: NM_018204
Type: single nucleotide variant
Location: chr13:52474977 (GRCh38)
Gene constraint: LOEUF 0.983 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.29

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

Similar variants

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
CKAP2 p.Ala614Ser 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-arg629cys (accessed [today's date]).

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