Is COPS6 p.Ser211Arg (c.631A>C) pathogenic?

COPS6 p.Ser211Arg (c.631A>C) is classified Uncertain significance in COPS6 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6163); Absent from gnomAD v4.1; Associated with prostate cancer.

What condition is associated with COPS6 p.Ser211Arg (c.631A>C)?

COPS6 p.Ser211Arg (c.631A>C) is associated with prostate cancer (ClinVar).

How common is COPS6 p.Ser211Arg (c.631A>C) in the general population?

COPS6 p.Ser211Arg (c.631A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPS6 p.Ser211Arg (c.631A>C)?

AlphaMissense predicts likely pathogenic (score 0.6163) — an in-silico prediction, not a clinical call.

COPS6 p.Ser211Arg

c.631A>C · rs193921011 · VCV161652

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6163 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.6163	likely pathogenic
REVEL	0.082	moderately benign-leaning
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 2,097 bp · p 7.5e-07 · regional, not allelic
Overall
CADD	22.1	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

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.Ser211Arg
Coding: c.631A>C
MANE Select: NM_006833
dbSNP: rs193921011
Type: single nucleotide variant
Location: chr7:100091134 (GRCh38)
Gene constraint: LOEUF 0.373 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 29 PDB
Residue 211: the 'interaction with vpr' region

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

Disease context

prostate cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
COPS6 p.Gly129Glu 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-ser211arg (accessed [today's date]).

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