Is DDC p.Ala78Ser (c.232G>T) pathogenic?

DDC p.Ala78Ser (c.232G>T) is classified Conflicting classifications of pathogenicity in DDC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-05). AlphaMissense: likely benign (0.2679); Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with DDC p.Ala78Ser (c.232G>T)?

DDC p.Ala78Ser (c.232G>T) is associated with Inborn genetic diseases, aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Ala78Ser (c.232G>T) in the general population?

DDC p.Ala78Ser (c.232G>T) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about DDC p.Ala78Ser (c.232G>T)?

AlphaMissense predicts likely benign (score 0.2679) — an in-silico prediction, not a clinical call.

DDC p.Ala78Ser

c.232G>T · rs140276979 · VCV949757

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2679	likely benign
REVEL	0.436	indeterminate
SaProt	LLR -10.68	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
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	26.9	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 0.00935% African / African-American · 7/74,874 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,740 alleles · very rare exomes 4/1,461,634 · genomes 3/152,106 · 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.Ala78Ser
Coding: c.232G>T
MANE Select: NM_001082971
dbSNP: rs140276979
Type: single nucleotide variant
Location: chr7:50539998 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 78: the '2 x approximate tandem repeats' region; a β-strand

Full DDC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: aromatic L-amino acid decarboxylase deficiency

Similar variants

DDC p.Ala78= Benign ★★ same residue
DDC p.Ala78Thr 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.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-ala78ser (accessed [today's date]).

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