Is ODC1 p.Val191Asp (c.572T>A) pathogenic?

ODC1 p.Val191Asp (c.572T>A) is classified Uncertain significance in ODC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9969); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with alopecia and brain abnormalities.

What condition is associated with ODC1 p.Val191Asp (c.572T>A)?

ODC1 p.Val191Asp (c.572T>A) is associated with neurodevelopmental disorder with alopecia and brain abnormalities (ClinVar).

How common is ODC1 p.Val191Asp (c.572T>A) in the general population?

ODC1 p.Val191Asp (c.572T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ODC1 p.Val191Asp (c.572T>A)?

AlphaMissense predicts likely pathogenic (score 0.9969) — an in-silico prediction, not a clinical call.

ODC1 p.Val191Asp

Q: How is Global developmental delay-alopecia-macrocephaly-facial dysmorphism-structural brain anomalies syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.572T>A · VCV4881944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with alopecia and brain abnormalities

Computational evidence

Protein change
AlphaMissense	0.9969	likely pathogenic · top 1% in ODC1
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -17.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1.9, phastCons 1
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Val191Asp
Coding: c.572T>A
MANE Select: NM_030631 · reported on NM_002539
Type: single nucleotide variant
Location: chr2:10443714 (GRCh38)
Structure: AlphaFold pLDDT 88.91

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

Disease context

neurodevelopmental disorder with alopecia and brain abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Global developmental delay-alopecia-macrocephaly-facial dysmorphism-structural brain anomalies syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Neonatal

Similar variants

ODC1 c.1242-2A>G Pathogenic ★★ same condition
ODC1 p.Trp443Ter Likely pathogenic ★ same condition
ODC1 p.Asn256Lys Uncertain significance ★ ⚠ same condition
ODC1 p.Asp304Glu Uncertain significance ★ ⚠ same condition
ODC1 p.Asp35Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
ODC1 p.Asp424Asn Uncertain significance ★ ⚠ same condition
ODC1 p.Met131Ile Uncertain significance ★ ⚠ same condition
ODC1 p.Thr396Met 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-val191asp (accessed [today's date]).

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