Is COPS2 p.Asp186Glu (c.558T>A) pathogenic?

COPS2 p.Asp186Glu (c.558T>A) is classified Uncertain significance in COPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely pathogenic (0.7003); Absent from gnomAD v4.1.

How common is COPS2 p.Asp186Glu (c.558T>A) in the general population?

COPS2 p.Asp186Glu (c.558T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPS2 p.Asp186Glu (c.558T>A)?

AlphaMissense predicts likely pathogenic (score 0.7003) — an in-silico prediction, not a clinical call.

COPS2 p.Asp186Glu

c.558T>A · VCV4005786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7003 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7003	likely pathogenic
REVEL	0.325	indeterminate
SaProt	LLR -5.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 21 kb · p 2.2e-19 · regional, not allelic
Overall
CADD	22.4	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: COPS2
Protein: p.Asp186Glu
Coding: c.558T>A
MANE Select: NM_004236
Type: single nucleotide variant
Location: chr15:49134497 (GRCh38)
Gene constraint: LOEUF 0.138 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.22 · 29 PDB
Residue 186: the 'mediates interaction with nif3l1' region

Full COPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS2 p.Pro47= Likely benign ★★ same type
COPS2 p.Ala419Gly Uncertain significance ★ ⚠ same type
COPS2 p.Ala419Thr Uncertain significance ★ ⚠ same type
COPS2 p.Ala49Val Uncertain significance ★ ⚠ same type
COPS2 p.Arg162Gln Uncertain significance ★ ⚠ same type
COPS2 p.Arg401Gln Uncertain significance ★ ⚠ same type
COPS2 p.Arg416Gly Uncertain significance ★ ⚠ same type
COPS2 p.Arg420Gln 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/cops2-p-asp186glu (accessed [today's date]).

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