Is COPS8 p.Gly73Arg (c.217G>A) pathogenic?

COPS8 p.Gly73Arg (c.217G>A) is classified Uncertain significance in COPS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.3419); Absent from gnomAD v4.1.

How common is COPS8 p.Gly73Arg (c.217G>A) in the general population?

COPS8 p.Gly73Arg (c.217G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPS8 p.Gly73Arg (c.217G>A)?

AlphaMissense predicts ambiguous (score 0.3419) — an in-silico prediction, not a clinical call.

COPS8 p.Gly73Arg

c.217G>A · VCV4655883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3419 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3419	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -9.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP -0.69, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 12 kb · p 0.012 · regional, not allelic
Overall
CADD	22.9	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: COPS8
Protein: p.Gly73Arg
Coding: c.217G>A
MANE Select: NM_006710
Type: single nucleotide variant
Location: chr2:237089880 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 85.78 · 28 PDB
Residue 73: the pci domain

Full COPS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS8 p.Ala119Gly Uncertain significance ★ ⚠ same type
COPS8 p.Ala119Thr Uncertain significance ★ ⚠ same type
COPS8 p.Ala144Val Uncertain significance ★ ⚠ same type
COPS8 p.Ala95Thr Uncertain significance ★ ⚠ same type
COPS8 p.Arg110Lys Uncertain significance ★ ⚠ same type
COPS8 p.Arg116Cys Uncertain significance ★ ⚠ same type
COPS8 p.Arg160Ser Uncertain significance ★ ⚠ same type
COPS8 p.Arg80Ser 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/cops8-p-gly73arg (accessed [today's date]).

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