Is ODC1 p.Pro346Ala (c.1036C>G) pathogenic?

ODC1 p.Pro346Ala (c.1036C>G) is classified Uncertain significance in ODC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.0647); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ODC1 p.Pro346Ala (c.1036C>G)?

ODC1 p.Pro346Ala (c.1036C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ODC1 p.Pro346Ala (c.1036C>G) in the general population?

ODC1 p.Pro346Ala (c.1036C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ODC1 p.Pro346Ala (c.1036C>G)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

ODC1 p.Pro346Ala

c.1036C>G · rs2528564870 · VCV2399831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -5.54	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 9.9	GERP 0.79, phastCons 1
Overall
CADD	21.6	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.Pro346Ala
Coding: c.1036C>G
MANE Select: NM_002539
dbSNP: rs2528564870
Type: single nucleotide variant
Location: chr2:10441714 (GRCh38)
Structure: AlphaFold pLDDT 88.91

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ODC1 p.Ile251Met Uncertain significance ★★ ⚠ same condition
ODC1 p.Pro264Leu Uncertain significance ★★ ⚠ same condition
ODC1 p.Ala258Val Likely benign ★★ same condition
ODC1 p.Gly253Arg Benign/Likely benign ★★ same condition
ODC1 c.1241+2T>G Uncertain significance ★ same condition
ODC1 p.Ala283Ser Uncertain significance ★ ⚠ same condition
ODC1 p.Ala413Val Uncertain significance ★ ⚠ same condition
ODC1 p.Arg165Cys Uncertain significance ★ ⚠ same condition

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-pro346ala (accessed [today's date]).

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