Is CKAP2L p.Arg263Ser (c.789A>T) pathogenic?

CKAP2L p.Arg263Ser (c.789A>T) is classified Benign in CKAP2L (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.2067); Common (popmax 18.1%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CKAP2L p.Arg263Ser (c.789A>T)?

AlphaMissense predicts likely benign (score 0.2067) — an in-silico prediction, not a clinical call.

CKAP2L p.Arg263Ser

Q: How common is CKAP2L p.Arg263Ser (c.789A>T) in the general population?

CKAP2L p.Arg263Ser (c.789A>T) is common (popmax 18.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.789A>T · rs17042341 · VCV1175564

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2067 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 18.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2067	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.91	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 0.25	GERP -0.96
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.21 · regional, not allelic
Overall
CADD	14.38	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 18.1% African / African-American · 13,542/74,788 alleles

Filtering AF 17.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.7%

Overall 5.21% 84,074/1,612,376 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.1%	6
Remaining individualsnot grpmax-eligible	5.44%	18
European (non-Finnish)	5.08%	20
Middle Eastern	5.04%	20
Admixed American	3.95%	25
Ashkenazi Jewishnot grpmax-eligible	3.77%	27
South Asian	2.26%	44
Finnishnot grpmax-eligible	2.11%	47
Amishnot grpmax-eligible	0.33%	303
East Asian	0.0111%	8,977

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.Arg263Ser
Coding: c.789A>T
MANE Select: NM_152515
dbSNP: rs17042341
Type: single nucleotide variant
Location: chr2:112756582 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68
Residue 263: a UniProt-annotated variant site (in); the 'disordered' region

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-arg263ser (accessed [today's date]).

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