Is COPS7B p.Lys164Gln (c.490A>C) pathogenic?

COPS7B p.Lys164Gln (c.490A>C) is classified Uncertain significance in COPS7B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.098); Absent from gnomAD v4.1.

How common is COPS7B p.Lys164Gln (c.490A>C) in the general population?

COPS7B p.Lys164Gln (c.490A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPS7B p.Lys164Gln (c.490A>C)?

AlphaMissense predicts likely benign (score 0.098) — an in-silico prediction, not a clinical call.

COPS7B p.Lys164Gln

c.490A>C · rs2469373515 · VCV2337491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.098 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.098	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -5.90	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 0.69, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 19 kb · p 2e-05 · regional, not allelic
Overall
CADD	21.4	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

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: COPS7B
Protein: p.Lys164Gln
Coding: c.490A>C
MANE Select: NM_022730
dbSNP: rs2469373515
Type: single nucleotide variant
Location: chr2:231796268 (GRCh38)
Gene constraint: LOEUF 0.517 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 85.00 · 25 PDB

Full COPS7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS7B p.Ala222Pro Uncertain significance ★ ⚠ same type
COPS7B p.Ala244Thr Uncertain significance ★ ⚠ same type
COPS7B p.Ala29Thr Uncertain significance ★ ⚠ same type
COPS7B p.Arg160Cys Uncertain significance ★ ⚠ same type
COPS7B p.Arg160His Uncertain significance ★ ⚠ same type
COPS7B p.Arg163Gly Uncertain significance ★ ⚠ same type
COPS7B p.Arg263His Uncertain significance ★ ⚠ same type
COPS7B p.Asn215Ile 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/cops7b-p-lys164gln (accessed [today's date]).

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