Is CKAP5 p.Arg1010Cys (c.3028C>T) pathogenic?

CKAP5 p.Arg1010Cys (c.3028C>T) is classified Uncertain significance in CKAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.2662); Very rare (popmax 0.00223%, eas).

How common is CKAP5 p.Arg1010Cys (c.3028C>T) in the general population?

CKAP5 p.Arg1010Cys (c.3028C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CKAP5 p.Arg1010Cys (c.3028C>T)?

AlphaMissense predicts likely benign (score 0.2662) — an in-silico prediction, not a clinical call.

CKAP5 p.Arg1010Cys

c.3028C>T · VCV4003211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2662 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2662	likely benign
REVEL	0.479	indeterminate
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Pangolin	Δ0.31	gain · loss 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 34 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	34.0	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 0.00223% East Asian · 1/44,898 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,702 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
South Asian	0.0011%	91,026
European (non-Finnish)	0.00017%	589,908

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.Arg1010Cys
Coding: c.3028C>T
MANE Select: NM_001008938
Type: single nucleotide variant
Location: chr11:46770946 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 3 PDB
Residue 1010: the 'tog 4' region

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

Similar variants

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CKAP5 p.Ala1127Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala124Ser Uncertain significance ★ ⚠ same type
CKAP5 p.Ala124Thr Uncertain significance ★ ⚠ same type
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CKAP5 p.Ala1429Gly 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/ckap5-p-arg1010cys (accessed [today's date]).

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