Is CKAP4 p.Pro44Leu (c.131C>T) pathogenic?

CKAP4 p.Pro44Leu (c.131C>T) is classified Uncertain significance in CKAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely benign (0.128); Very rare (popmax 0.00695%, afr).

How common is CKAP4 p.Pro44Leu (c.131C>T) in the general population?

CKAP4 p.Pro44Leu (c.131C>T) is very rare (popmax 0.00695%, afr) (gnomAD).

What do computational predictors say about CKAP4 p.Pro44Leu (c.131C>T)?

AlphaMissense predicts likely benign (score 0.128) — an in-silico prediction, not a clinical call.

CKAP4 p.Pro44Leu

c.131C>T · rs1203205240 · VCV3145214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.128	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -9.80	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 2.1	GERP 0.46, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 7,648 bp · p 0.029 · regional, not allelic
Overall
CADD	16.41	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 0.00695% African / African-American · 4/57,556 alleles

Filtering AF 0.0051% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00466%

Overall 0.00604% 63/1,043,722 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00695%	14,389
European (non-Finnish)	0.00652%	15,327
South Asian	0.00429%	23,318
Remaining individualsnot grpmax-eligible	0.00304%	32,894

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: CKAP4
Protein: p.Pro44Leu
Coding: c.131C>T
MANE Select: NM_006825
dbSNP: rs1203205240
Type: single nucleotide variant
Location: chr12:106247721 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.61
Residue 44: the 'disordered' region

Full CKAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP4 p.His444= Benign ★★ same type
CKAP4 p.Leu580Val Benign ★★ same type
CKAP4 p.Thr236= Benign ★★ same type
CKAP4 p.Tyr483= Likely benign ★★ same type
CKAP4 p.Ala167Gly Uncertain significance ★ ⚠ same type
CKAP4 p.Ala23Gly Uncertain significance ★ ⚠ same type
CKAP4 p.Ala449Thr Uncertain significance ★ ⚠ same type
CKAP4 p.Ala522Thr 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/ckap4-p-pro44leu (accessed [today's date]).

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