Is ODC1 p.Tyr331fs (c.991dup) pathogenic?

ODC1 p.Tyr331fs (c.991dup) is classified Uncertain significance in ODC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-05). Very rare (popmax 8.47e-05%, nfe); Associated with ODC1-related disorder.

What condition is associated with ODC1 p.Tyr331fs (c.991dup)?

ODC1 p.Tyr331fs (c.991dup) is associated with ODC1-related disorder (ClinVar).

How common is ODC1 p.Tyr331fs (c.991dup) in the general population?

ODC1 p.Tyr331fs (c.991dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ODC1 p.Tyr331fs

c.991dup · rs2528565818 · VCV2631622

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

ODC1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 0.81, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,004 alleles

Overall 6.84e-05% 1/1,461,846 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: ODC1
Protein: p.Tyr331fs
Coding: c.991dup
MANE Select: NM_030631 · reported on NM_002539
dbSNP: rs2528565818
Type: Duplication
Location: chr2:10441851 (GRCh38)
Structure: AlphaFold pLDDT 88.91

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

Disease context

ODC1-related disorder

Similar variants

ODC1 p.Tyr406Phe Uncertain significance ★ ⚠ same condition
ODC1 p.Val192Ala Uncertain significance ★ ⚠ same condition
ODC1 p.Ser309Leu Likely benign same condition
ODC1 p.Trp356fs Likely pathogenic ★ same type
ODC1 p.Asn289fs Uncertain significance ★ same type
ODC1 p.Phe65fs Uncertain significance ★ same type
ODC1 p.Ser167fs Uncertain significance ★ same type
SLC25A21 c.839-20dup 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-tyr331fs (accessed [today's date]).

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