Is COPG1 p.Phe5Ser (c.14T>C) pathogenic?

COPG1 p.Phe5Ser (c.14T>C) is classified Uncertain significance in COPG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.2799); Very rare (popmax 0.00244%, eas).

How common is COPG1 p.Phe5Ser (c.14T>C) in the general population?

COPG1 p.Phe5Ser (c.14T>C) is very rare (popmax 0.00244%, eas) (gnomAD).

What do computational predictors say about COPG1 p.Phe5Ser (c.14T>C)?

AlphaMissense predicts likely benign (score 0.2799) — an in-silico prediction, not a clinical call.

COPG1 p.Phe5Ser

c.14T>C · rs2530334014 · VCV3076245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2799 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2799	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -5.97	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 1.3, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 28 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	26.5	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 0.00244% East Asian · 1/40,914 alleles

Overall 7.15e-05% 1/1,399,214 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.Phe5Ser
Coding: c.14T>C
MANE Select: NM_016128
dbSNP: rs2530334014
Type: single nucleotide variant
Location: chr3:129249723 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.09 · 1 PDB
Residue 5: the 'disordered' region

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-phe5ser (accessed [today's date]).

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