Is DDC p.Arg285Trp (c.853C>T) pathogenic?

DDC p.Arg285Trp (c.853C>T) is classified Conflicting classifications of pathogenicity in DDC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-10). AlphaMissense: ambiguous (0.5247); Very rare (popmax 0.00223%, eas); Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Arg285Trp (c.853C>T)?

DDC p.Arg285Trp (c.853C>T) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Arg285Trp (c.853C>T) in the general population?

DDC p.Arg285Trp (c.853C>T) is very rare (popmax 0.00223%, 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.

What do computational predictors say about DDC p.Arg285Trp (c.853C>T)?

AlphaMissense predicts ambiguous (score 0.5247) — an in-silico prediction, not a clinical call.

DDC p.Arg285Trp

c.853C>T · rs886062372 · VCV360433

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5247 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

aromatic L-amino acid decarboxylase deficiency

Computational evidence

Protein change
AlphaMissense	0.5247	ambiguous
REVEL	0.593	indeterminate
SaProt	LLR -14.27	damaging
Splicing
SpliceAI	Δ0.24	donor loss, 23 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.6	GERP 0.67, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,752 alleles · very rare exomes 4/1,461,590 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
European (non-Finnish)	0.000339%	294,964

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.Arg285Trp
Coding: c.853C>T
MANE Select: NM_001082971
dbSNP: rs886062372
Type: single nucleotide variant
Location: chr7:50499171 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 285: 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.Arg285Gln Uncertain significance ★★ ⚠ same residue
DDC p.Arg285= Likely benign ★ 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-arg285trp (accessed [today's date]).

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