Is CKAP5 p.Asn573Ser (c.1718A>G) pathogenic?

CKAP5 p.Asn573Ser (c.1718A>G) is classified Uncertain significance in CKAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.0561); Very rare (popmax 0.005%, amr).

How common is CKAP5 p.Asn573Ser (c.1718A>G) in the general population?

CKAP5 p.Asn573Ser (c.1718A>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CKAP5 p.Asn573Ser (c.1718A>G)?

AlphaMissense predicts likely benign (score 0.0561) — an in-silico prediction, not a clinical call.

CKAP5 p.Asn573Ser

c.1718A>G · rs1221553326 · VCV2238078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0561 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0561	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -5.07	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 -0.38	GERP -4.8, phastCons 0.2
Regional constraint	o/e 0.80	unconstrained · MANE · 34 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	12.81	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 0.005% Admixed American · 3/59,988 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00198% 32/1,614,024 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,996
European (non-Finnish)	0.00246%	40,690

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.Asn573Ser
Coding: c.1718A>G
MANE Select: NM_001008938
dbSNP: rs1221553326
Type: single nucleotide variant
Location: chr11:46790516 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 3 PDB
Residue 573: the 'disordered' region

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

Similar variants

CKAP5 c.4569-2A>G Uncertain significance ★ same type
CKAP5 p.Ala1041Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala1099Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala1127Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala124Ser Uncertain significance ★ ⚠ same type
CKAP5 p.Ala124Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala1386Ser Uncertain significance ★ ⚠ same type
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-asn573ser (accessed [today's date]).

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