Is DDC p.Arg397His (c.1190G>A) pathogenic?

DDC p.Arg397His (c.1190G>A) is classified Uncertain significance in DDC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-05). AlphaMissense: likely benign (0.1811); Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with DDC p.Arg397His (c.1190G>A)?

DDC p.Arg397His (c.1190G>A) is associated with Inborn genetic diseases, aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Arg397His (c.1190G>A) in the general population?

DDC p.Arg397His (c.1190G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about DDC p.Arg397His (c.1190G>A)?

AlphaMissense predicts likely benign (score 0.1811) — an in-silico prediction, not a clinical call.

DDC p.Arg397His

c.1190G>A · rs144293557 · VCV360430

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1811 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1811	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.39, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,874 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00291% 47/1,614,128 alleles · ultra-rare exomes 41/1,461,836 · genomes 6/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,975
European (non-Finnish)	0.00331%	30,256
South Asian	0.0022%	45,539
Admixed American	0.00167%	60,028

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.Arg397His
Coding: c.1190G>A
MANE Select: NM_001082971
dbSNP: rs144293557
Type: single nucleotide variant
Location: chr7:50467266 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB

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.Arg397Cys 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
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-arg397his (accessed [today's date]).

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