Is CKAP2L p.Ser388Leu (c.1163C>T) pathogenic?

CKAP2L p.Ser388Leu (c.1163C>T) is classified Uncertain significance in CKAP2L (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-27). AlphaMissense: likely benign (0.0861); Ultra-rare (popmax 0.0267%, amr); Associated with Inborn genetic diseases.

What condition is associated with CKAP2L p.Ser388Leu (c.1163C>T)?

CKAP2L p.Ser388Leu (c.1163C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CKAP2L p.Ser388Leu (c.1163C>T) in the general population?

CKAP2L p.Ser388Leu (c.1163C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about CKAP2L p.Ser388Leu (c.1163C>T)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

CKAP2L p.Ser388Leu

c.1163C>T · rs563147561 · VCV2046532

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -8.17	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 7.1	GERP 2.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	21.8	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 0.0267% Admixed American · 16/60,030 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00204% 33/1,614,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,752
South Asian	0.00878%	11,385
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.000508%	196,671

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.Ser388Leu
Coding: c.1163C>T
MANE Select: NM_152515
dbSNP: rs563147561
Type: single nucleotide variant
Location: chr2:112756208 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68
Residue 388: 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.Ser388Pro 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-ser388leu (accessed [today's date]).

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