Is DDC p.Arg160Trp (c.478C>T) pathogenic?

DDC p.Arg160Trp (c.478C>T) is classified Pathogenic/Likely pathogenic in DDC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-10). AlphaMissense: likely pathogenic (0.9017); Very rare (popmax 0.00133%, afr); Associated with DDC-related disorder.

What condition is associated with DDC p.Arg160Trp (c.478C>T)?

DDC p.Arg160Trp (c.478C>T) is associated with DDC-related disorder, aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Arg160Trp (c.478C>T) in the general population?

DDC p.Arg160Trp (c.478C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DDC p.Arg160Trp (c.478C>T)?

AlphaMissense predicts likely pathogenic (score 0.9017) — an in-silico prediction, not a clinical call.

DDC p.Arg160Trp

c.478C>T · rs886062374 · VCV360437

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9017 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DDC-related disorder

Computational evidence

Protein change
AlphaMissense	0.9017	likely pathogenic ✓ concordant with ClinVar
REVEL	0.648	pathogenic-leaning
SaProt	LLR -15.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	28.4	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 0.00133% African / African-American · 1/74,926 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,042 alleles · very rare exomes 3/1,461,836 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,926
South Asian	0.0011%	91,082
European (non-Finnish)	0.000169%	590,019

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.Arg160Trp
Coding: c.478C>T
MANE Select: NM_001082971
dbSNP: rs886062374
Type: single nucleotide variant
Location: chr7:50529300 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 160: 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

DDC-related disorder

Also linked: aromatic L-amino acid decarboxylase deficiency

Similar variants

DDC p.Arg160Gln Uncertain significance ★★ same residue
DDC p.Arg160= 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-arg160trp (accessed [today's date]).

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