Is COPS6 p.Val242Phe (c.724G>T) pathogenic?

COPS6 p.Val242Phe (c.724G>T) is classified Uncertain significance in COPS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.8146); Absent from gnomAD v4.1.

How common is COPS6 p.Val242Phe (c.724G>T) in the general population?

COPS6 p.Val242Phe (c.724G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPS6 p.Val242Phe (c.724G>T)?

AlphaMissense predicts likely pathogenic (score 0.8146) — an in-silico prediction, not a clinical call.

COPS6 p.Val242Phe

c.724G>T · VCV3495999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8146 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8146	likely pathogenic
REVEL	0.336	indeterminate
SaProt	LLR -10.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.93	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 0.97, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 2,097 bp · p 7.5e-07 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: COPS6
Protein: p.Val242Phe
Coding: c.724G>T
MANE Select: NM_006833
Type: single nucleotide variant
Location: chr7:100091312 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 29 PDB
Residue 242: the 'interaction with vpr' region

Full COPS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS6 p.Val242Ile Uncertain significance ★ ⚠ same residue
COPS6 p.Ala290Thr Uncertain significance ★ ⚠ same type
COPS6 p.Ala42Val Uncertain significance ★ ⚠ same type
COPS6 p.Ala7Val Uncertain significance ★ ⚠ same type
COPS6 p.Asn307Lys Uncertain significance ★ ⚠ same type
COPS6 p.Asp101Glu Uncertain significance ★ ⚠ same type
COPS6 p.Asp173Gly Uncertain significance ★ ⚠ same type
COPS6 p.Glu240Ala 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/cops6-p-val242phe (accessed [today's date]).

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