Is COPS2 p.Asp15Asn (c.43G>A) pathogenic?

COPS2 p.Asp15Asn (c.43G>A) is classified Uncertain significance in COPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely benign (0.2937); Very rare (popmax 8.47e-05%, nfe).

How common is COPS2 p.Asp15Asn (c.43G>A) in the general population?

COPS2 p.Asp15Asn (c.43G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about COPS2 p.Asp15Asn (c.43G>A)?

AlphaMissense predicts likely benign (score 0.2937) — an in-silico prediction, not a clinical call.

COPS2 p.Asp15Asn

c.43G>A · rs2504759206 · VCV3076267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2937 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2937	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 6.1, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 48 bp · p 0.24 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.84e-05% 1/1,461,848 alleles · very rare

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.Asp15Asn
Coding: c.43G>A
MANE Select: NM_004236
dbSNP: rs2504759206
Type: single nucleotide variant
Location: chr15:49155536 (GRCh38)
Gene constraint: LOEUF 0.138 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.22 · 29 PDB
Residue 15: 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-asp15asn (accessed [today's date]).

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