Is CKAP2L p.Pro279Ala (c.835C>G) pathogenic?

CKAP2L p.Pro279Ala (c.835C>G) is classified Uncertain significance in CKAP2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.0923); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CKAP2L p.Pro279Ala (c.835C>G)?

CKAP2L p.Pro279Ala (c.835C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CKAP2L p.Pro279Ala (c.835C>G) in the general population?

CKAP2L p.Pro279Ala (c.835C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CKAP2L p.Pro279Ala (c.835C>G)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

CKAP2L p.Pro279Ala

c.835C>G · VCV3493125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.28	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 1.7	GERP -2.4, phastCons 0.96
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	14.75	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 0.0165% Middle Eastern · 1/6,044 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,609,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,044
European (non-Finnish)	0.00204%	49,097

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.Pro279Ala
Coding: c.835C>G
MANE Select: NM_152515
Type: single nucleotide variant
Location: chr2:112756536 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CKAP2L p.Pro279Arg Uncertain significance ★ ⚠ same residue
CKAP2L p.Arg206Gly Uncertain significance ★★ ⚠ same condition
CKAP2L p.Arg284Trp Uncertain significance ★★ ⚠ same condition
CKAP2L p.Arg688Gln Uncertain significance ★★ ⚠ same condition
CKAP2L p.Gln428Arg Uncertain significance ★★ ⚠ same condition
CKAP2L p.Ile283Leu Uncertain significance ★★ ⚠ same condition
CKAP2L p.Lys421Arg Uncertain significance ★★ ⚠ same condition
CKAP2L p.Lys480Glu Uncertain significance ★★ ⚠ same condition

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-pro279ala (accessed [today's date]).

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