Is ODC1 p.Val192Ala (c.575T>C) pathogenic?

ODC1 p.Val192Ala (c.575T>C) is classified Uncertain significance in ODC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely benign (0.2331); Very rare (popmax 0.0022%, sas); Associated with ODC1-related disorder.

What condition is associated with ODC1 p.Val192Ala (c.575T>C)?

ODC1 p.Val192Ala (c.575T>C) is associated with ODC1-related disorder (ClinVar).

How common is ODC1 p.Val192Ala (c.575T>C) in the general population?

ODC1 p.Val192Ala (c.575T>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ODC1 p.Val192Ala (c.575T>C)?

AlphaMissense predicts likely benign (score 0.2331) — an in-silico prediction, not a clinical call.

ODC1 p.Val192Ala

c.575T>C · rs1301787958 · VCV2635918

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2331 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ODC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.2331	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -8.40	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 11	GERP 0.93, phastCons 1
Overall
CADD	25.0	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

Grpmax group 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000205% 3/1,461,826 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
African / African-American	0.00133%	75,050

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.Val192Ala
Coding: c.575T>C
MANE Select: NM_030631 · reported on NM_002539
dbSNP: rs1301787958
Type: single nucleotide variant
Location: chr2:10443711 (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.Ser309Leu Likely benign same condition
ODC1 p.Tyr331fs Uncertain significance ★ same condition
ODC1 c.1242-2A>G Pathogenic ★★ same type
ODC1 p.Ile251Met Uncertain significance ★★ ⚠ same type
ODC1 p.Pro264Leu Uncertain significance ★★ ⚠ same type
SLC25A21 p.Ala113Thr Uncertain significance ★★ ⚠ same type
SLC25A21 p.Glu95Asp 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/odc1-p-val192ala (accessed [today's date]).

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