Is CSN3 p.Pro170Arg (c.509C>G) pathogenic?

CSN3 p.Pro170Arg (c.509C>G) is classified Uncertain significance in CSN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.2459); Very rare (popmax 8.47e-05%, nfe).

How common is CSN3 p.Pro170Arg (c.509C>G) in the general population?

CSN3 p.Pro170Arg (c.509C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CSN3 p.Pro170Arg (c.509C>G)?

AlphaMissense predicts likely benign (score 0.2459) — an in-silico prediction, not a clinical call.

CSN3 p.Pro170Arg

c.509C>G · rs1730443151 · VCV3078263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2459 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2459	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 0.96
Overall
CADD	16.81	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,954 alleles

Overall 6.84e-05% 1/1,461,700 alleles · very rare

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: CSN3
Protein: p.Pro170Arg
Coding: c.509C>G
MANE Select: NM_003653 · reported on NM_001394997
dbSNP: rs1730443151
Type: single nucleotide variant
Location: chr4:70249419 (GRCh38)
Structure: AlphaFold pLDDT 84.64 · 28 PDB

Full CSN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS3 p.Ala371Gly Uncertain significance ★ ⚠ same type
COPS3 p.Arg119Gln Uncertain significance ★ ⚠ same type
COPS3 p.Asn109Ile Uncertain significance ★ ⚠ same type
COPS3 p.Gln308Arg Uncertain significance ★ ⚠ same type
COPS3 p.Gln82His Uncertain significance ★ ⚠ same type
COPS3 p.Glu75Lys Uncertain significance ★ ⚠ same type
COPS3 p.Ile228Thr Uncertain significance ★ ⚠ same type
COPS3 p.Ile351Val 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/csn3-p-pro170arg (accessed [today's date]).

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