Is ODC1 p.Arg449Cys (c.1345C>T) pathogenic?

ODC1 p.Arg449Cys (c.1345C>T) is classified Likely benign in ODC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely benign (0.082); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with ODC1 p.Arg449Cys (c.1345C>T)?

ODC1 p.Arg449Cys (c.1345C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ODC1 p.Arg449Cys (c.1345C>T) in the general population?

ODC1 p.Arg449Cys (c.1345C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about ODC1 p.Arg449Cys (c.1345C>T)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

ODC1 p.Arg449Cys

c.1345C>T · VCV3302171

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -7.34	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 3.8	GERP 0.91, phastCons 0.75
Regional constraint	o/e 0.85	unconstrained · MANE · 3,850 bp · p 0.00073 · regional, not allelic
Overall
CADD	21.5	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 0.0117% Admixed American · 7/60,014 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00167% 27/1,614,052 alleles · ultra-rare exomes 27/1,461,868 · genomes 0/152,184 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.00144%	69,412
South Asian	0.0011%	91,068

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: ODC1
Protein: p.Arg449Cys
Coding: c.1345C>T
MANE Select: NM_002539
Type: single nucleotide variant
Location: chr2:10440765 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.23 (gnomAD)
Structure: AlphaFold pLDDT 88.30 · 11 PDB
Residue 449: a UniProt-annotated variant site (in babs); a UniProt-annotated variant site (in babs; gain-of-function variant resulting in increased putrescine biosynthesis as indicated by higher amount of putrescine in patient red blood cells compared to controls; increased odc1 protein levels in patient red blood cells)

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-arg449cys (accessed [today's date]).

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