Is COPS2 p.Val439Asp (c.1316T>A) pathogenic?

COPS2 p.Val439Asp (c.1316T>A) is classified Uncertain significance in COPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.5998); Ultra-rare (popmax 0.02%, amr).

How common is COPS2 p.Val439Asp (c.1316T>A) in the general population?

COPS2 p.Val439Asp (c.1316T>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about COPS2 p.Val439Asp (c.1316T>A)?

AlphaMissense predicts likely pathogenic (score 0.5998) — an in-silico prediction, not a clinical call.

COPS2 p.Val439Asp

c.1316T>A · rs769677428 · VCV3076266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5998 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5998	likely pathogenic
REVEL	0.302	indeterminate
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 750 bp · p 0.063 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.02% Admixed American · 12/59,986 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000868% 14/1,613,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,999
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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.Val439Asp
Coding: c.1316T>A
MANE Select: NM_004236
dbSNP: rs769677428
Type: single nucleotide variant
Location: chr15:49127966 (GRCh38)
Gene constraint: LOEUF 0.138 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.22 · 29 PDB

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-val439asp (accessed [today's date]).

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