Is CKAP2L p.Val60Ile (c.178G>A) pathogenic?

CKAP2L p.Val60Ile (c.178G>A) is classified Uncertain significance in CKAP2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). AlphaMissense: likely benign (0.0746); Very rare (popmax 0.00978%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CKAP2L p.Val60Ile (c.178G>A)?

CKAP2L p.Val60Ile (c.178G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CKAP2L p.Val60Ile (c.178G>A) in the general population?

CKAP2L p.Val60Ile (c.178G>A) is very rare (popmax 0.00978%, nfe) (gnomAD).

What do computational predictors say about CKAP2L p.Val60Ile (c.178G>A)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

CKAP2L p.Val60Ile

c.178G>A · rs370676547 · VCV2360033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00978%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.65	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 0.019	GERP -2.7, phastCons 0.6
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	13.08	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 0.00978% European (non-Finnish) · 115/1,176,418 alleles

Filtering AF 0.00828% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00776%

Overall 0.00759% 122/1,606,976 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00978%	10,230
African / African-American	0.00537%	18,618
Remaining individualsnot grpmax-eligible	0.00483%	20,723

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.Val60Ile
Coding: c.178G>A
MANE Select: NM_152515
dbSNP: rs370676547
Type: single nucleotide variant
Location: chr2:112757193 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68
Residue 60: the 'disordered' region

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.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
CKAP2L p.Pro670Ser 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-val60ile (accessed [today's date]).

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