Is COPG1 p.Pro38Ser (c.112C>T) pathogenic?

COPG1 p.Pro38Ser (c.112C>T) is classified Uncertain significance in COPG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: likely pathogenic (0.7555); Very rare (popmax 0.00167%, amr).

How common is COPG1 p.Pro38Ser (c.112C>T) in the general population?

COPG1 p.Pro38Ser (c.112C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about COPG1 p.Pro38Ser (c.112C>T)?

AlphaMissense predicts likely pathogenic (score 0.7555) — an in-silico prediction, not a clinical call.

COPG1 p.Pro38Ser

c.112C>T · rs1428685967 · VCV2281655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7555	likely pathogenic
REVEL	0.367	indeterminate
SaProt	LLR -10.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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 0.77	unconstrained · MANE · 28 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	27.3	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

Grpmax group 0.00167% Admixed American · 1/60,002 alleles

Overall 6.85e-05% 1/1,459,850 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: COPG1
Protein: p.Pro38Ser
Coding: c.112C>T
MANE Select: NM_016128
dbSNP: rs1428685967
Type: single nucleotide variant
Location: chr3:129252302 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.09 · 1 PDB

Full COPG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPG1 p.Arg247His Uncertain significance ★★ ⚠ same type
COPG1 p.Leu864Met Uncertain significance ★★ ⚠ same type
COPG1 p.Thr64Met Uncertain significance ★★ ⚠ same type
COPG1 c.91-11T>C Benign ★★ same type
COPG1 c.939+13C>G Benign ★★ same type
COPG1 p.His221= Benign ★★ same type
COPG1 p.Ile92= Benign/Likely benign ★★ same type
COPG1 p.Leu240Val Benign/Likely benign ★★ ⚠ 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/copg1-p-pro38ser (accessed [today's date]).

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