Is DDC p.Ala91= (c.273G>A) pathogenic?

DDC p.Ala91= (c.273G>A) is classified Likely benign in DDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-13). Ultra-rare (popmax 0.0691%, eas); Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Ala91= (c.273G>A)?

DDC p.Ala91= (c.273G>A) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Ala91= (c.273G>A) in the general population?

DDC p.Ala91= (c.273G>A) is ultra-rare (popmax 0.0691%, eas) (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.Ala91=

c.273G>A · rs561069897 · VCV2082457

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0691%, eas)

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	0.113	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5.1
Overall
CADD	0.321	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0691% East Asian · 31/44,858 alleles

Filtering AF 0.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0435%

Overall 0.00403% 65/1,614,016 alleles · ultra-rare exomes 61/1,461,742 · genomes 4/152,274 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0691%	1,447
South Asian	0.0165%	6,071
Remaining individualsnot grpmax-eligible	0.0032%	31,251
Admixed American	0.00167%	60,012
Finnishnot grpmax-eligible	0.00156%	63,988
European (non-Finnish)	0.00127%	78,666

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.Ala91=
Coding: c.273G>A
MANE Select: NM_001082971
dbSNP: rs561069897
Type: single nucleotide variant
Location: chr7:50539957 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 91: a UniProt-annotated variant site (in aadcd); the '2 x approximate tandem repeats' region; an α-helix

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.Ala91Val Pathogenic/Likely pathogenic ★★ same residue
DDC p.Ala91_Leu94dup 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.Arg160Trp 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-ala91 (accessed [today's date]).

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