Is DDC p.Met17Val (c.49A>G) pathogenic?

DDC p.Met17Val (c.49A>G) is classified Benign/Likely benign in DDC (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-04-03). AlphaMissense: likely benign (0.0651); Common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Met17Val (c.49A>G)?

DDC p.Met17Val (c.49A>G) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

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.Met17Val (c.49A>G)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

DDC p.Met17Val

Q: How common is DDC p.Met17Val (c.49A>G) in the general population?

DDC p.Met17Val (c.49A>G) is common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.49A>G · rs6264 · VCV1168240

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aromatic L-amino acid decarboxylase deficiency

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -4.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.72	GERP -5.3
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	0.236	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 100% European (non-Finnish) · 1,179,984/1,180,044 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.9% 1,612,416/1,614,208 alleles · common exomes 1,460,939/1,461,878 · genomes 151,477/152,330 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
Finnishnot grpmax-eligible	100%	1
European (non-Finnish)grpmax	100%	1
East Asian	100%	1
South Asian	100%	1
Middle Eastern	99.9%	1
Admixed American	99.9%	1
Remaining individualsnot grpmax-eligible	99.9%	1
African / African-American	97.9%	1

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met17Val
Coding: c.49A>G
MANE Select: NM_001082971
dbSNP: rs6264
Type: single nucleotide variant
Location: chr7:50544037 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 17: a UniProt-annotated variant site (in); 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.Met17= 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-met17val (accessed [today's date]).

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