Is DDC p.Cys100Ser (c.299G>C) pathogenic?

DDC p.Cys100Ser (c.299G>C) is classified Likely pathogenic in DDC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). AlphaMissense: ambiguous (0.4487); Very rare (popmax 0.000678%, nfe); Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Cys100Ser (c.299G>C)?

DDC p.Cys100Ser (c.299G>C) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Cys100Ser (c.299G>C) in the general population?

DDC p.Cys100Ser (c.299G>C) is very rare (popmax 0.000678%, nfe) (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.Cys100Ser (c.299G>C)?

AlphaMissense predicts ambiguous (score 0.4487) — an in-silico prediction, not a clinical call.

DDC p.Cys100Ser

c.299G>C · rs200339845 · VCV1917800

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4487 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

aromatic L-amino acid decarboxylase deficiency

Computational evidence

Protein change
AlphaMissense	0.4487	ambiguous
REVEL	0.394	indeterminate
SaProt	LLR -9.93	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	27.2	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 0.000678% European (non-Finnish) · 8/1,179,838 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,792 alleles · very rare exomes 8/1,461,506 · genomes 0/152,286 · joint denominator

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.Cys100Ser
Coding: c.299G>C
MANE Select: NM_001082971
dbSNP: rs200339845
Type: single nucleotide variant
Location: chr7:50539931 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 100: the '2 x approximate tandem repeats' region

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.Cys100= 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
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-cys100ser (accessed [today's date]).

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