Is COPS2 p.Asn304Ser (c.911A>G) pathogenic?

COPS2 p.Asn304Ser (c.911A>G) is classified Uncertain significance in COPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely benign (0.1395); Absent from gnomAD v4.1.

How common is COPS2 p.Asn304Ser (c.911A>G) in the general population?

COPS2 p.Asn304Ser (c.911A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPS2 p.Asn304Ser (c.911A>G)?

AlphaMissense predicts likely benign (score 0.1395) — an in-silico prediction, not a clinical call.

COPS2 p.Asn304Ser

c.911A>G · rs2504732585 · VCV3076269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1395 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1395	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -5.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 5,374 bp · p 4.5e-19 · regional, not allelic
Overall
CADD	22.1	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

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.Asn304Ser
Coding: c.911A>G
MANE Select: NM_004236
dbSNP: rs2504732585
Type: single nucleotide variant
Location: chr15:49133795 (GRCh38)
Gene constraint: LOEUF 0.138 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.22 · 29 PDB
Residue 304: 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-asn304ser (accessed [today's date]).

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