Is CKAP5 p.Pro1130Ser (c.3388C>T) pathogenic?

CKAP5 p.Pro1130Ser (c.3388C>T) is classified Uncertain significance in CKAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0544); Very rare (popmax 0.000424%, nfe).

How common is CKAP5 p.Pro1130Ser (c.3388C>T) in the general population?

CKAP5 p.Pro1130Ser (c.3388C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CKAP5 p.Pro1130Ser (c.3388C>T)?

AlphaMissense predicts likely benign (score 0.0544) — an in-silico prediction, not a clinical call.

CKAP5 p.Pro1130Ser

c.3388C>T · VCV4229257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0544	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.92	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 2.2	GERP -2.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 34 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	13.81	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 0.000424% European (non-Finnish) · 5/1,178,892 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,232 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.Pro1130Ser
Coding: c.3388C>T
MANE Select: NM_001008938
Type: single nucleotide variant
Location: chr11:46767598 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 3 PDB
Residue 1130: 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-pro1130ser (accessed [today's date]).

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