Is CRACD p.Arg288Pro (c.863G>C) pathogenic?

CRACD p.Arg288Pro (c.863G>C) is classified Uncertain significance in CRACD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-30). AlphaMissense: likely benign (0.089); Very rare (popmax 8.72e-05%, nfe).

How common is CRACD p.Arg288Pro (c.863G>C) in the general population?

CRACD p.Arg288Pro (c.863G>C) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about CRACD p.Arg288Pro (c.863G>C)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

CRACD p.Arg288Pro

c.863G>C · rs1005568978 · VCV2614762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.30	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 -4.5	GERP -2.9
Regional constraint	o/e 1.09	unconstrained · MANE · 25 kb · p 0.00032 · regional, not allelic
Overall
CADD	0.036	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 8.72e-05% European (non-Finnish) · 1/1,146,300 alleles

Overall 7.16e-05% 1/1,396,064 alleles · very 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: CRACD
Protein: p.Arg288Pro
Coding: c.863G>C
MANE Select: NM_001393381
dbSNP: rs1005568978
Type: single nucleotide variant
Location: chr4:56314365 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.09
Residue 288: the 'disordered' region

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

Similar variants

CRACD p.Ala1035Gly Uncertain significance ★ ⚠ same type
CRACD p.Ala1105Val Uncertain significance ★ ⚠ same type
CRACD p.Ala1116Asp Uncertain significance ★ ⚠ same type
CRACD p.Ala1149Pro Uncertain significance ★ ⚠ same type
CRACD p.Ala1149Val Uncertain significance ★ ⚠ same type
CRACD p.Ala1190Val Uncertain significance ★ ⚠ same type
CRACD p.Ala283Val Uncertain significance ★ ⚠ same type
CRACD p.Ala303Thr 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/cracd-p-arg288pro (accessed [today's date]).

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