Is DDC p.Pro43= (c.129T>C) pathogenic?

DDC p.Pro43= (c.129T>C) is classified Likely benign in DDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 0.004%, afr); Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Pro43= (c.129T>C)?

DDC p.Pro43= (c.129T>C) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Pro43= (c.129T>C) in the general population?

DDC p.Pro43= (c.129T>C) is very rare (popmax 0.004%, afr) (gnomAD).

How is Aromatic L-amino acid decarboxylase deficiency inherited?

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

DDC p.Pro43=

c.129T>C · rs1288457534 · VCV1913167

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

aromatic L-amino acid decarboxylase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.153	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -5.3
Overall
CADD	1.808	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,908 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,614,044 alleles · very rare exomes 4/1,461,882 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,969
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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: DDC
Protein: p.Pro43=
Coding: c.129T>C
MANE Select: NM_001082971
dbSNP: rs1288457534
Type: single nucleotide variant
Location: chr7:50543957 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB

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.Pro43Arg Uncertain significance ★ same residue
DDC p.Pro43fs Pathogenic/Likely pathogenic ★★ 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-pro43 (accessed [today's date]).

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