Is ODC1 p.Pro438Ser (c.1312C>T) pathogenic?

ODC1 p.Pro438Ser (c.1312C>T) is classified Uncertain significance in ODC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely benign (0.1165); Absent from gnomAD v4.1.

How common is ODC1 p.Pro438Ser (c.1312C>T) in the general population?

ODC1 p.Pro438Ser (c.1312C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ODC1 p.Pro438Ser (c.1312C>T)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

ODC1 p.Pro438Ser

c.1312C>T · rs753193727 · VCV2582119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -5.88	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 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 3,850 bp · p 0.00073 · regional, not allelic
Overall
CADD	23.9	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

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: ODC1
Protein: p.Pro438Ser
Coding: c.1312C>T
MANE Select: NM_002539
dbSNP: rs753193727
Type: single nucleotide variant
Location: chr2:10440798 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.23 (gnomAD)
Structure: AlphaFold pLDDT 88.30 · 11 PDB
Residue 438: a UniProt-annotated variant site (in babs)

Full ODC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ODC1 p.Pro438fs Likely pathogenic ★ same residue
ODC1 c.1242-2A>G Pathogenic ★★ same type
ODC1 p.Ile251Met Uncertain significance ★★ ⚠ same type
ODC1 p.Pro264Leu Uncertain significance ★★ ⚠ same type
ODC1 p.Ala258Val Likely benign ★★ same type
ODC1 p.Gly253Arg Benign/Likely benign ★★ same type
ODC1 p.Gly84Arg Likely benign ★★ ⚠ same type
ODC1 p.Pro423= 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/odc1-p-pro438ser (accessed [today's date]).

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