Is COPS3 p.Ser70Thr (c.209G>C) pathogenic?

COPS3 p.Ser70Thr (c.209G>C) is classified Uncertain significance in COPS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-14). AlphaMissense: likely benign (0.0619); Very rare (popmax 0.0072%, nfe).

How common is COPS3 p.Ser70Thr (c.209G>C) in the general population?

COPS3 p.Ser70Thr (c.209G>C) is very rare (popmax 0.0072%, nfe) (gnomAD).

What do computational predictors say about COPS3 p.Ser70Thr (c.209G>C)?

AlphaMissense predicts likely benign (score 0.0619) — an in-silico prediction, not a clinical call.

COPS3 p.Ser70Thr

c.209G>C · rs370739274 · VCV2216354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0619	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.31	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 34 kb · p 4.5e-15 · regional, not allelic
Overall
CADD	22.4	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

Grpmax group 0.0072% European (non-Finnish) · 85/1,179,900 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00533% 86/1,613,786 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0072%	13,881
African / African-American	0.00134%	74,886

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: COPS3
Protein: p.Ser70Thr
Coding: c.209G>C
MANE Select: NM_003653
dbSNP: rs370739274
Type: single nucleotide variant
Location: chr17:17270985 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.64 · 28 PDB

Full COPS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS3 p.Ser70Asn Uncertain significance ★ ⚠ same residue
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

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/cops3-p-ser70thr (accessed [today's date]).

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