Is COPS4 p.Ile29Val (c.85A>G) pathogenic?

COPS4 p.Ile29Val (c.85A>G) is classified Uncertain significance in COPS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.0785); Very rare (popmax 0.00267%, afr).

How common is COPS4 p.Ile29Val (c.85A>G) in the general population?

COPS4 p.Ile29Val (c.85A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about COPS4 p.Ile29Val (c.85A>G)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

COPS4 p.Ile29Val

c.85A>G · VCV4232818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -5.87	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.32 · regional, not allelic
Overall
CADD	21.1	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

Grpmax group 0.00267% African / African-American · 2/74,870 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000744% 12/1,612,516 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,435
European (non-Finnish)	0.000848%	117,894

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: COPS4
Protein: p.Ile29Val
Coding: c.85A>G
MANE Select: NM_016129
Type: single nucleotide variant
Location: chr4:83045636 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.79 · 29 PDB
Residue 29: an α-helix

Full COPS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS4 p.Ala10Ser Uncertain significance ★ ⚠ same type
COPS4 p.Ala4Val Uncertain significance ★ ⚠ same type
COPS4 p.Arg27Cys Uncertain significance ★ ⚠ same type
COPS4 p.Arg27His Uncertain significance ★ ⚠ same type
COPS4 p.Arg27Pro Uncertain significance ★ ⚠ same type
COPS4 p.Arg364Gln Uncertain significance ★ ⚠ same type
COPS4 p.Asn180Ser Uncertain significance ★ ⚠ same type
COPS4 p.Asp8Gly 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/cops4-p-ile29val (accessed [today's date]).

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