Is CROCC p.Arg1007Gln (c.3020G>A) pathogenic?

CROCC p.Arg1007Gln (c.3020G>A) is classified Uncertain significance in CROCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely benign (0.0703); Rare (popmax 0.159%, afr).

How common is CROCC p.Arg1007Gln (c.3020G>A) in the general population?

CROCC p.Arg1007Gln (c.3020G>A) is rare (popmax 0.159%, afr) (gnomAD).

What do computational predictors say about CROCC p.Arg1007Gln (c.3020G>A)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CROCC p.Arg1007Gln

c.3020G>A · VCV3836445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.159%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.52	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 2.2	GERP 1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,470 bp · p 0.074 · regional, not allelic
Overall
CADD	21.1	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 0.159% African / African-American · 119/74,616 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.0121% 193/1,588,706 alleles · rare exomes 123/1,436,356 · genomes 70/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.159%	627
Remaining individualsnot grpmax-eligible	0.0147%	6,823
Admixed American	0.0124%	8,039
East Asian	0.00687%	14,558
European (non-Finnish)	0.00462%	21,661
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,112

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.Arg1007Gln
Coding: c.3020G>A
MANE Select: NM_014675
Type: single nucleotide variant
Location: chr1:16953315 (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.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
CROCC p.Arg903Ser Benign/Likely 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-arg1007gln (accessed [today's date]).

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