Is CKAP4 p.Ser195Arg (c.585T>A) pathogenic?

CKAP4 p.Ser195Arg (c.585T>A) is classified Uncertain significance in CKAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: ambiguous (0.3494); Rare (popmax 0.495%, mid).

How common is CKAP4 p.Ser195Arg (c.585T>A) in the general population?

CKAP4 p.Ser195Arg (c.585T>A) is rare (popmax 0.495%, mid) (gnomAD).

What do computational predictors say about CKAP4 p.Ser195Arg (c.585T>A)?

AlphaMissense predicts ambiguous (score 0.3494) — an in-silico prediction, not a clinical call.

CKAP4 p.Ser195Arg

c.585T>A · rs183401520 · VCV3145224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3494 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.495%, mid)

Computational evidence

Protein change
AlphaMissense	0.3494	ambiguous
REVEL	0.387	indeterminate
SaProt	LLR -7.17	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -4
Regional constraint	o/e 1.13	unconstrained · MANE · 7,648 bp · p 0.029 · regional, not allelic
Overall
CADD	7.919	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 0.495% Middle Eastern · 30/6,060 alleles

Filtering AF 0.356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.309%

Overall 0.00979% 158/1,613,214 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.495%	202
South Asian	0.0494%	2,023
Remaining individualsnot grpmax-eligible	0.024%	4,166
African / African-American	0.00937%	10,674
Admixed American	0.00501%	19,976
European (non-Finnish)	0.00492%	20,341

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: CKAP4
Protein: p.Ser195Arg
Coding: c.585T>A
MANE Select: NM_006825
dbSNP: rs183401520
Type: single nucleotide variant
Location: chr12:106240248 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.61

Full CKAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP4 p.His444= Benign ★★ same type
CKAP4 p.Leu580Val Benign ★★ same type
CKAP4 p.Thr236= Benign ★★ same type
CKAP4 p.Tyr483= Likely benign ★★ same type
CKAP4 p.Ala167Gly Uncertain significance ★ ⚠ same type
CKAP4 p.Ala23Gly Uncertain significance ★ ⚠ same type
CKAP4 p.Ala449Thr Uncertain significance ★ ⚠ same type
CKAP4 p.Ala522Thr 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/ckap4-p-ser195arg (accessed [today's date]).

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