Is CROCC p.Arg784Trp (c.2350C>T) pathogenic?

CROCC p.Arg784Trp (c.2350C>T) is classified Uncertain significance in CROCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.1016); Ultra-rare (popmax 0.0121%, eas).

How common is CROCC p.Arg784Trp (c.2350C>T) in the general population?

CROCC p.Arg784Trp (c.2350C>T) is ultra-rare (popmax 0.0121%, eas) (gnomAD).

What do computational predictors say about CROCC p.Arg784Trp (c.2350C>T)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

CROCC p.Arg784Trp

c.2350C>T · VCV4656746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -11.27	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 -0.29	GERP -2.7
Regional constraint	o/e 1.22	unconstrained · MANE · 2,882 bp · p 0.00061 · regional, not allelic
Overall
CADD	16.27	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 0.0121% East Asian · 5/41,174 alleles

Filtering AF 0.00476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00307%

Overall 0.00135% 21/1,553,540 alleles · ultra-rare exomes 18/1,401,130 · genomes 3/152,410 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0121%	8,235
African / African-American	0.00409%	24,469
Admixed American	0.00196%	51,114
South Asian	0.00119%	84,178
European (non-Finnish)	0.000958%	104,386

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: CROCC
Protein: p.Arg784Trp
Coding: c.2350C>T
MANE Select: NM_014675
Type: single nucleotide variant
Location: chr1:16946827 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 2 PDB

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

Similar variants

CROCC p.Arg784Gln Uncertain significance ★ ⚠ same residue
CROCC p.Arg1094Trp Uncertain significance ★★ ⚠ same type
CROCC p.Asp1119His Uncertain significance ★★ ⚠ same type
CROCC p.Gly486Arg Uncertain significance ★★ ⚠ same type
CROCC p.Arg1729Gln Likely benign ★★ same type
CROCC p.Arg1908Cys Benign ★★ ⚠ same type
CROCC p.Arg675His Benign ★★ same type
CROCC p.Arg691His Benign ★★ 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/crocc-p-arg784trp (accessed [today's date]).

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