Is DDC p.Pro47Thr (c.139C>A) pathogenic?

DDC p.Pro47Thr (c.139C>A) is classified Uncertain significance in DDC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-20). AlphaMissense: likely pathogenic (0.6701); Absent from gnomAD v4.1; Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Pro47Thr (c.139C>A)?

DDC p.Pro47Thr (c.139C>A) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Pro47Thr (c.139C>A) in the general population?

DDC p.Pro47Thr (c.139C>A) is absent from gnomAD v4.1 (gnomAD).

How is Aromatic L-amino acid decarboxylase deficiency inherited?

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

What do computational predictors say about DDC p.Pro47Thr (c.139C>A)?

AlphaMissense predicts likely pathogenic (score 0.6701) — an in-silico prediction, not a clinical call.

DDC p.Pro47Thr

c.139C>A · rs2535520536 · VCV2100208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6701 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

aromatic L-amino acid decarboxylase deficiency

Computational evidence

Protein change
AlphaMissense	0.6701	likely pathogenic
REVEL	0.633	indeterminate
SaProt	LLR -13.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	25.4	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: DDC
Protein: p.Pro47Thr
Coding: c.139C>A
MANE Select: NM_001082971
dbSNP: rs2535520536
Type: single nucleotide variant
Location: chr7:50543947 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 47: a UniProt-annotated variant site (in aadcd)

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

Disease context

aromatic L-amino acid decarboxylase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Aromatic L-amino acid decarboxylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DDC p.Pro47His Pathogenic/Likely pathogenic ★★ same residue
DDC p.Pro47Ala Uncertain significance ★ same residue
DDC c.1041+1G>A Pathogenic/Likely pathogenic ★★ same condition
DDC c.201+1G>C Likely pathogenic ★★ same condition
DDC c.201+5G>C Pathogenic/Likely pathogenic ★★ same condition
DDC c.714+4A>T Pathogenic ★★ same condition
DDC p.Ala275Thr Pathogenic/Likely pathogenic ★★ same condition
DDC p.Ala91Val Pathogenic/Likely pathogenic ★★ 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/ddc-p-pro47thr (accessed [today's date]).

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