Is CKAP2L p.Pro4Ser (c.10C>T) pathogenic?

CKAP2L p.Pro4Ser (c.10C>T) is classified Uncertain significance in CKAP2L (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely benign (0.1229); Ultra-rare (popmax 0.0133%, nfe).

How common is CKAP2L p.Pro4Ser (c.10C>T) in the general population?

CKAP2L p.Pro4Ser (c.10C>T) is ultra-rare (popmax 0.0133%, nfe) (gnomAD).

What do computational predictors say about CKAP2L p.Pro4Ser (c.10C>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

CKAP2L p.Pro4Ser

c.10C>T · rs143626181 · VCV2708684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.45	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 1.3	GERP -2.6, phastCons 0.8
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	13.57	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 0.0133% European (non-Finnish) · 157/1,180,024 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0102% 165/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0133%	7,516
Remaining individualsnot grpmax-eligible	0.0064%	15,619
Admixed American	0.005%	20,005
South Asian	0.0011%	91,090

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: CKAP2L
Protein: p.Pro4Ser
Coding: c.10C>T
MANE Select: NM_152515
dbSNP: rs143626181
Type: single nucleotide variant
Location: chr2:112764589 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68

Full CKAP2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP2L p.Arg206Gly Uncertain significance ★★ ⚠ same type
CKAP2L p.Arg284Trp Uncertain significance ★★ ⚠ same type
CKAP2L p.Arg347Lys Uncertain significance ★★ ⚠ same type
CKAP2L p.Arg688Gln Uncertain significance ★★ ⚠ same type
CKAP2L p.Cys725Ser Uncertain significance ★★ ⚠ same type
CKAP2L p.Gln428Arg Uncertain significance ★★ ⚠ same type
CKAP2L p.Glu462Val Uncertain significance ★★ ⚠ same type
CKAP2L p.Ile283Leu 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/ckap2l-p-pro4ser (accessed [today's date]).

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