Is COPS7A p.Val115Met (c.343G>A) pathogenic?

COPS7A p.Val115Met (c.343G>A) is classified Uncertain significance in COPS7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: likely benign (0.1832); Very rare (popmax 0.00333%, amr).

How common is COPS7A p.Val115Met (c.343G>A) in the general population?

COPS7A p.Val115Met (c.343G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about COPS7A p.Val115Met (c.343G>A)?

AlphaMissense predicts likely benign (score 0.1832) — an in-silico prediction, not a clinical call.

COPS7A p.Val115Met

c.343G>A · VCV4655875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1832 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1832	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.74	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 6,379 bp · p 7.1e-08 · regional, not allelic
Overall
CADD	32.0	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 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,164 alleles · very rare exomes 2/1,461,892 · genomes 0/152,272 · joint denominator

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: COPS7A
Protein: p.Val115Met
Coding: c.343G>A
MANE Select: NM_001164094
Type: single nucleotide variant
Location: chr12:6729262 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.98 · 3 PDB
Residue 115: the pci domain

Full COPS7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS7A p.Val115Leu Uncertain significance ★ ⚠ same residue
COPS7A p.Met49Leu Uncertain significance ★★ ⚠ same type
COPS7A p.Ala19Gly Uncertain significance ★ ⚠ same type
COPS7A p.Ala229Ser Uncertain significance ★ ⚠ same type
COPS7A p.Ala229Thr Uncertain significance ★ ⚠ same type
COPS7A p.Ala258Val Uncertain significance ★ ⚠ same type
COPS7A p.Ala26Ser Uncertain significance ★ same type
COPS7A p.Ala37Thr 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/cops7a-p-val115met (accessed [today's date]).

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