Is CKAP5 p.Pro1159Arg (c.3476C>G) pathogenic?

CKAP5 p.Pro1159Arg (c.3476C>G) is classified Uncertain significance in CKAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: ambiguous (0.5331); Very rare (popmax 0.0044%, sas).

How common is CKAP5 p.Pro1159Arg (c.3476C>G) in the general population?

CKAP5 p.Pro1159Arg (c.3476C>G) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about CKAP5 p.Pro1159Arg (c.3476C>G)?

AlphaMissense predicts ambiguous (score 0.5331) — an in-silico prediction, not a clinical call.

CKAP5 p.Pro1159Arg

c.3476C>G · VCV4653997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5331 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Computational evidence

Protein change
AlphaMissense	0.5331	ambiguous
REVEL	0.482	indeterminate
SaProt	LLR -9.19	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 34 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% South Asian · 4/90,884 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.000274% 4/1,460,362 alleles · very rare

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.Pro1159Arg
Coding: c.3476C>G
MANE Select: NM_001008938
Type: single nucleotide variant
Location: chr11:46765192 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 3 PDB
Residue 1159: 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-pro1159arg (accessed [today's date]).

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