Is CPOX p.Pro313Thr (c.937C>A) pathogenic?

CPOX p.Pro313Thr (c.937C>A) is classified Uncertain significance in CPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-10). AlphaMissense: likely benign (0.096); Very rare (popmax 0.000169%, nfe).

How common is CPOX p.Pro313Thr (c.937C>A) in the general population?

CPOX p.Pro313Thr (c.937C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CPOX p.Pro313Thr (c.937C>A)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

CPOX p.Pro313Thr

c.937C>A · rs2107126046 · VCV1306846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -11.61	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 10 kb · p 7.6e-05 · regional, not allelic
Overall
CADD	29.9	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,858 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: CPOX
Protein: p.Pro313Thr
Coding: c.937C>A
MANE Select: NM_000097
dbSNP: rs2107126046
Type: single nucleotide variant
Location: chr3:98588729 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 1 PDB
Residue 313: 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.Pro313Arg Uncertain significance ★ ⚠ same residue
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

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-pro313thr (accessed [today's date]).

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