Is DDC p.Ala272= (c.816A>C) pathogenic?

DDC p.Ala272= (c.816A>C) is classified Conflicting classifications of pathogenicity in DDC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-19). Ultra-rare (popmax 0.0495%, mid); Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Ala272= (c.816A>C)?

DDC p.Ala272= (c.816A>C) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Ala272= (c.816A>C) in the general population?

DDC p.Ala272= (c.816A>C) is ultra-rare (popmax 0.0495%, mid) (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.Ala272=

c.816A>C · rs767990522 · VCV753732

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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	0.068	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.4	GERP -5.2
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00397% 64/1,613,874 alleles · ultra-rare exomes 55/1,461,548 · genomes 9/152,326 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.115%	871
Middle Easterngrpmax	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00333%	30,009
European (non-Finnish)	0.00153%	65,554
African / African-American	0.00133%	75,050

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala272=
Coding: c.816A>C
MANE Select: NM_001082971
dbSNP: rs767990522
Type: single nucleotide variant
Location: chr7:50499208 (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 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
DDC p.Arg160Trp Pathogenic/Likely pathogenic ★★ same condition
DDC p.Arg347Gln 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-ala272 (accessed [today's date]).

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