Is COP1 p.Lys507Glu (c.1519A>G) pathogenic?

COP1 p.Lys507Glu (c.1519A>G) is classified Uncertain significance in COP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely pathogenic (0.8627); Absent from gnomAD v4.1.

How common is COP1 p.Lys507Glu (c.1519A>G) in the general population?

COP1 p.Lys507Glu (c.1519A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COP1 p.Lys507Glu (c.1519A>G)?

AlphaMissense predicts likely pathogenic (score 0.8627) — an in-silico prediction, not a clinical call.

COP1 p.Lys507Glu

c.1519A>G · VCV3495942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8627	likely pathogenic
REVEL	0.34	indeterminate
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 136 kb · p 5.4e-19 · regional, not allelic
Overall
CADD	30.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COP1
Protein: p.Lys507Glu
Coding: c.1519A>G
MANE Select: NM_022457
Type: single nucleotide variant
Location: chr1:176043721 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 75.64 · 7 PDB
Residue 507: a β-strand

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-lys507glu (accessed [today's date]).

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