Is COP1 p.Arg384Gln (c.1151G>A) pathogenic?

COP1 p.Arg384Gln (c.1151G>A) is classified Uncertain significance in COP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely benign (0.1327); Rare (popmax 0.136%, mid).

How common is COP1 p.Arg384Gln (c.1151G>A) in the general population?

COP1 p.Arg384Gln (c.1151G>A) is rare (popmax 0.136%, mid) (gnomAD).

What do computational predictors say about COP1 p.Arg384Gln (c.1151G>A)?

AlphaMissense predicts likely benign (score 0.1327) — an in-silico prediction, not a clinical call.

COP1 p.Arg384Gln

c.1151G>A · rs148950158 · VCV2530270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1327 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1327	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -6.04	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 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 83 kb · p 0.064 · regional, not allelic
Overall
CADD	29.6	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 0.136% Middle Eastern · 8/5,886 alleles

Filtering AF 0.0676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0493%

Overall 0.0193% 303/1,570,962 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.136%	736
Remaining individualsnot grpmax-eligible	0.0346%	2,893
East Asian	0.0272%	3,682
European (non-Finnish)	0.0213%	4,689
Admixed American	0.0129%	7,782
South Asian	0.00581%	17,202
African / African-American	0.00282%	35,416
Finnishnot grpmax-eligible	0.00164%	60,958

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: COP1
Protein: p.Arg384Gln
Coding: c.1151G>A
MANE Select: NM_022457
dbSNP: rs148950158
Type: single nucleotide variant
Location: chr1:176081278 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 75.64 · 7 PDB

Full COP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COP1 c.1142-7C>T Likely benign ★★ same type
COP1 p.Arg295Thr Benign ★★ ⚠ same type
COP1 p.Met299Val Benign ★★ same type
COP1 p.Ala117Val Uncertain significance ★ ⚠ same type
COP1 p.Ala12Ser Uncertain significance ★ ⚠ same type
COP1 p.Ala354Val Uncertain significance ★ ⚠ same type
COP1 p.Ala457Val Uncertain significance ★ ⚠ same type
COP1 p.Ala7Val 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/cop1-p-arg384gln (accessed [today's date]).

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