Is CKAP2L p.Ser213Pro (c.637T>C) pathogenic?

CKAP2L p.Ser213Pro (c.637T>C) is classified Likely benign in CKAP2L (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.1004); Ultra-rare (popmax 0.0803%, eas); Associated with CKAP2L-related disorder.

What condition is associated with CKAP2L p.Ser213Pro (c.637T>C)?

CKAP2L p.Ser213Pro (c.637T>C) is associated with CKAP2L-related disorder (ClinVar).

How common is CKAP2L p.Ser213Pro (c.637T>C) in the general population?

CKAP2L p.Ser213Pro (c.637T>C) is ultra-rare (popmax 0.0803%, eas) (gnomAD).

What do computational predictors say about CKAP2L p.Ser213Pro (c.637T>C)?

AlphaMissense predicts likely benign (score 0.1004) — an in-silico prediction, not a clinical call.

CKAP2L p.Ser213Pro

c.637T>C · rs767835982 · VCV3054735

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1004 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0803%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CKAP2L-related disorder

Computational evidence

Protein change
AlphaMissense	0.1004	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -6.99	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	GERP 0.92, phastCons 0.002
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	15.85	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0803% East Asian · 36/44,850 alleles

Filtering AF 0.0596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00275% 44/1,597,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0803%	1,246
Remaining individualsnot grpmax-eligible	0.013%	7,704

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.Ser213Pro
Coding: c.637T>C
MANE Select: NM_152515
dbSNP: rs767835982
Type: single nucleotide variant
Location: chr2:112756734 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68
Residue 213: the 'disordered' region

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

Disease context

CKAP2L-related disorder

Similar variants

CKAP2L p.Glu14Ter Likely pathogenic same condition
CKAP2L p.Arg319Gln Uncertain significance ⚠ same condition
CKAP2L p.Gly140= Likely benign same condition
CKAP2L p.Gln364fs Pathogenic/Likely pathogenic ★★ same condition
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

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-ser213pro (accessed [today's date]).

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