Is CKAP5 p.Phe231Cys (c.692T>G) pathogenic?

CKAP5 p.Phe231Cys (c.692T>G) is classified Uncertain significance in CKAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). AlphaMissense: ambiguous (0.5325); Ultra-rare (popmax 0.0107%, afr).

How common is CKAP5 p.Phe231Cys (c.692T>G) in the general population?

CKAP5 p.Phe231Cys (c.692T>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CKAP5 p.Phe231Cys (c.692T>G)?

AlphaMissense predicts ambiguous (score 0.5325) — an in-silico prediction, not a clinical call.

CKAP5 p.Phe231Cys

c.692T>G · rs777042989 · VCV3145245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5325 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Computational evidence

Protein change
AlphaMissense	0.5325	ambiguous
REVEL	0.36	indeterminate
SaProt	LLR -6.49	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 12 kb · p 0.39 · regional, not allelic
Overall
CADD	24.9	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 0.0107% African / African-American · 8/74,928 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,614,004 alleles · ultra-rare

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: CKAP5
Protein: p.Phe231Cys
Coding: c.692T>G
MANE Select: NM_001008938
dbSNP: rs777042989
Type: single nucleotide variant
Location: chr11:46809813 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 3 PDB

Full CKAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CKAP5 c.4569-2A>G Uncertain significance ★ same type
CKAP5 p.Ala1041Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala1099Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala1127Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala124Ser Uncertain significance ★ ⚠ same type
CKAP5 p.Ala124Thr Uncertain significance ★ ⚠ same type
CKAP5 p.Ala1386Ser Uncertain significance ★ ⚠ same type
CKAP5 p.Ala1429Gly 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/ckap5-p-phe231cys (accessed [today's date]).

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