Is CKAP4 p.Ser83Phe (c.248C>T) pathogenic?

CKAP4 p.Ser83Phe (c.248C>T) is classified Uncertain significance in CKAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.2324); Very rare (popmax 0.00583%, amr).

How common is CKAP4 p.Ser83Phe (c.248C>T) in the general population?

CKAP4 p.Ser83Phe (c.248C>T) is very rare (popmax 0.00583%, amr) (gnomAD).

What do computational predictors say about CKAP4 p.Ser83Phe (c.248C>T)?

AlphaMissense predicts likely benign (score 0.2324) — an in-silico prediction, not a clinical call.

CKAP4 p.Ser83Phe

c.248C>T · rs1182101037 · VCV2594707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2324 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00583%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2324	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -12.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP 0.23, phastCons 0.033
Regional constraint	o/e 1.13	unconstrained · MANE · 7,648 bp · p 0.029 · regional, not allelic
Overall
CADD	12.77	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 0.00583% Admixed American · 2/34,280 alleles

Filtering AF 0.00126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00102%

Overall 0.00186% 25/1,343,148 alleles · very rare exomes 20/1,196,194 · genomes 5/146,954 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00583%	17,140
Remaining individualsnot grpmax-eligible	0.00402%	24,847
European (non-Finnish)	0.00192%	52,022
African / African-American	0.00154%	64,968

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.Ser83Phe
Coding: c.248C>T
MANE Select: NM_006825
dbSNP: rs1182101037
Type: single nucleotide variant
Location: chr12:106247604 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.61
Residue 83: the 'disordered' region

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-ser83phe (accessed [today's date]).

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