Is CPOX p.Ser208Phe (c.623C>T) pathogenic?

CPOX p.Ser208Phe (c.623C>T) is classified Pathogenic in CPOX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2002-01-01). AlphaMissense: likely pathogenic (0.9838); Absent from gnomAD v4.1; Associated with Coproporphyria.

What condition is associated with CPOX p.Ser208Phe (c.623C>T)?

CPOX p.Ser208Phe (c.623C>T) is associated with Coproporphyria (ClinVar).

How common is CPOX p.Ser208Phe (c.623C>T) in the general population?

CPOX p.Ser208Phe (c.623C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPOX p.Ser208Phe (c.623C>T)?

AlphaMissense predicts likely pathogenic (score 0.9838) — an in-silico prediction, not a clinical call.

CPOX p.Ser208Phe

c.623C>T · rs121917872 · VCV460

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9838 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Coproporphyria

Computational evidence

Protein change
AlphaMissense	0.9838	likely pathogenic ✓ concordant with ClinVar · top 7% in CPOX
REVEL	0.968	strongly pathogenic-leaning
SaProt	LLR -13.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,476 bp · p 0.32 · regional, not allelic
Overall
CADD	33.0	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.Ser208Phe
Coding: c.623C>T
MANE Select: NM_000097
dbSNP: rs121917872
Type: single nucleotide variant
Location: chr3:98591089 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 1 PDB
Residue 208: a UniProt-annotated variant site (in hcp); a β-strand

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

Disease context

Coproporphyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPOX p.Arg328Cys Pathogenic same condition
CPOX p.Arg426Gln Pathogenic ⚠ same condition
CPOX p.Gln29Ter Pathogenic same condition
CPOX p.His295Asp Pathogenic ⚠ same condition
CPOX p.Cys164_Val170del Pathogenic same condition
CPOX p.Thr286fs Pathogenic same condition
CPOX p.Cys239Ter Pathogenic ★★ same type
CPOX p.Gln160Ter Pathogenic ★★ 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-ser208phe (accessed [today's date]).

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