Is CPOX p.Cys127Phe (c.380G>T) pathogenic?

CPOX p.Cys127Phe (c.380G>T) is classified Uncertain significance in CPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.2424); Absent from gnomAD v4.1.

How common is CPOX p.Cys127Phe (c.380G>T) in the general population?

CPOX p.Cys127Phe (c.380G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPOX p.Cys127Phe (c.380G>T)?

AlphaMissense predicts likely benign (score 0.2424) — an in-silico prediction, not a clinical call.

CPOX p.Cys127Phe

c.380G>T · VCV3657802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2424 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2424	likely benign
REVEL	0.679	pathogenic-leaning
SaProt	LLR -5.17	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,476 bp · p 0.32 · regional, not allelic
Overall
CADD	23.9	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: CPOX
Protein: p.Cys127Phe
Coding: c.380G>T
MANE Select: NM_000097
Type: single nucleotide variant
Location: chr3:98593125 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 1 PDB
Residue 127: a UniProt-annotated variant site (in hcp); an α-helix

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

Similar variants

CPOX p.Cys239Ter Pathogenic ★★ same type
CPOX p.Gln160Ter Pathogenic ★★ same type
CPOX p.Glu201Lys Pathogenic/Likely pathogenic ★★ same type
CPOX p.Lys404Glu Pathogenic/Likely pathogenic ★★ same type
CPOX c.811+5G>C Uncertain significance ★★ same type
CPOX p.Ala293Thr Uncertain significance ★★ ⚠ same type
CPOX p.Ala83Val Uncertain significance ★★ ⚠ same type
CPOX p.Ala89Val 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/cpox-p-cys127phe (accessed [today's date]).

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