Is CKAP2 p.Arg674Trp (c.2020C>T) pathogenic?

CKAP2 p.Arg674Trp (c.2020C>T) is classified Uncertain significance in CKAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1482); Rare (popmax 0.119%, sas).

How common is CKAP2 p.Arg674Trp (c.2020C>T) in the general population?

CKAP2 p.Arg674Trp (c.2020C>T) is rare (popmax 0.119%, sas) (gnomAD).

What do computational predictors say about CKAP2 p.Arg674Trp (c.2020C>T)?

AlphaMissense predicts likely benign (score 0.1482) — an in-silico prediction, not a clinical call.

CKAP2 p.Arg674Trp

c.2020C>T · rs202031498 · VCV3145196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1482 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1482	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -10.09	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -3.7
Regional constraint	o/e 0.98	unconstrained · MANE · 9,828 bp · p 0.79 · regional, not allelic
Overall
CADD	14.91	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 R675W vs ClinVar R674W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.119% South Asian · 108/91,054 alleles

Filtering AF 0.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0937%

Overall 0.00967% 156/1,614,060 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.119%	843
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.00314%	31,892
African / African-American	0.00267%	37,507
Admixed American	0.00167%	60,018
Finnishnot grpmax-eligible	0.00156%	64,010

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.Arg674Trp
Coding: c.2020C>T
MANE Select: NM_018204
dbSNP: rs202031498
Type: single nucleotide variant
Location: chr13:52475112 (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-arg674trp (accessed [today's date]).

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