Is COPS2 p.Glu307Gln (c.919G>C) pathogenic?

COPS2 p.Glu307Gln (c.919G>C) is classified Uncertain significance in COPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.5671); Very rare (popmax 0.0057%, nfe).

How common is COPS2 p.Glu307Gln (c.919G>C) in the general population?

COPS2 p.Glu307Gln (c.919G>C) is very rare (popmax 0.0057%, nfe) (gnomAD).

What do computational predictors say about COPS2 p.Glu307Gln (c.919G>C)?

AlphaMissense predicts likely pathogenic (score 0.5671) — an in-silico prediction, not a clinical call.

COPS2 p.Glu307Gln

c.919G>C · VCV4005783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0057%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5671	likely pathogenic
REVEL	0.344	indeterminate
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 5,374 bp · p 4.5e-19 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0057% European (non-Finnish) · 67/1,176,068 alleles

Filtering AF 0.00455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00418%

Overall 0.00424% 68/1,602,540 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0057%	17,553
Remaining individualsnot grpmax-eligible	0.00161%	62,018

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: COPS2
Protein: p.Glu307Gln
Coding: c.919G>C
MANE Select: NM_004236
Type: single nucleotide variant
Location: chr15:49133787 (GRCh38)
Gene constraint: LOEUF 0.138 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.22 · 29 PDB
Residue 307: the pci domain

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-glu307gln (accessed [today's date]).

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