Is DDC p.Ala78= (c.234C>T) pathogenic?

DDC p.Ala78= (c.234C>T) is classified Benign in DDC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 14.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Ala78= (c.234C>T)?

DDC p.Ala78= (c.234C>T) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

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.Ala78=

Q: How common is DDC p.Ala78= (c.234C>T) in the general population?

DDC p.Ala78= (c.234C>T) is common (popmax 14.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.234C>T · rs11575302 · VCV360441

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 14.3%, afr) — too common for a highly-penetrant pathogenic allele

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	0.074	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -1.7, phastCons 1
Overall
CADD	14.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.3% African / African-American · 10,708/74,968 alleles

Filtering AF 14.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 14%

Overall 2.13% 34,437/1,613,830 alleles · common exomes 26,873/1,461,570 · genomes 7,564/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.3%	7
Remaining individualsnot grpmax-eligible	2.32%	43
European (non-Finnish)	1.63%	62
Admixed American	1.49%	67
South Asian	1.44%	69
Amishnot grpmax-eligible	1.32%	76
Middle Eastern	1.29%	78
Finnishnot grpmax-eligible	0.866%	115
Ashkenazi Jewishnot grpmax-eligible	0.838%	119
East Asian	0.00668%	14,960

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.Ala78=
Coding: c.234C>T
MANE Select: NM_001082971
dbSNP: rs11575302
Type: single nucleotide variant
Location: chr7:50539996 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 78: the '2 x approximate tandem repeats' region; a β-strand

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.Ala78Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
DDC p.Ala78Thr 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-ala78 (accessed [today's date]).

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