Is CRACD p.Arg305Pro (c.914G>C) pathogenic?

CRACD p.Arg305Pro (c.914G>C) is classified Uncertain significance in CRACD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.1639); Ultra-rare (popmax 0.0133%, nfe).

How common is CRACD p.Arg305Pro (c.914G>C) in the general population?

CRACD p.Arg305Pro (c.914G>C) is ultra-rare (popmax 0.0133%, nfe) (gnomAD).

What do computational predictors say about CRACD p.Arg305Pro (c.914G>C)?

AlphaMissense predicts likely benign (score 0.1639) — an in-silico prediction, not a clinical call.

CRACD p.Arg305Pro

c.914G>C · rs941888807 · VCV3077141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1639	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -13.77	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 -4.3	GERP -3
Regional constraint	o/e 1.09	unconstrained · MANE · 25 kb · p 0.00032 · regional, not allelic
Overall
CADD	1.683	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 0.0133% European (non-Finnish) · 152/1,144,772 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0103% 159/1,544,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0133%	7,531
Remaining individualsnot grpmax-eligible	0.00838%	11,934
East Asian	0.00245%	40,846
African / African-American	0.00137%	72,768

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.Arg305Pro
Coding: c.914G>C
MANE Select: NM_001393381
dbSNP: rs941888807
Type: single nucleotide variant
Location: chr4:56314416 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.09
Residue 305: 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-arg305pro (accessed [today's date]).

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