Is CKAP4 p.His511Asp (c.1531C>G) pathogenic?

CKAP4 p.His511Asp (c.1531C>G) is classified Uncertain significance in CKAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.206); Very rare (popmax 0.00769%, sas).

How common is CKAP4 p.His511Asp (c.1531C>G) in the general population?

CKAP4 p.His511Asp (c.1531C>G) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about CKAP4 p.His511Asp (c.1531C>G)?

AlphaMissense predicts likely benign (score 0.206) — an in-silico prediction, not a clinical call.

CKAP4 p.His511Asp

c.1531C>G · VCV4653977

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.206	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -5.09	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 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,007 bp · p 0.25 · regional, not allelic
Overall
CADD	20.5	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 0.00769% South Asian · 7/91,082 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000497% 8/1,611,168 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.His511Asp
Coding: c.1531C>G
MANE Select: NM_006825
Type: single nucleotide variant
Location: chr12:106239302 (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-his511asp (accessed [today's date]).

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