Is DDC p.Ala225Asp (c.674C>A) pathogenic?

DDC p.Ala225Asp (c.674C>A) is classified Uncertain significance in DDC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.3216); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DDC p.Ala225Asp (c.674C>A)?

DDC p.Ala225Asp (c.674C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DDC p.Ala225Asp (c.674C>A) in the general population?

DDC p.Ala225Asp (c.674C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about DDC p.Ala225Asp (c.674C>A)?

AlphaMissense predicts likely benign (score 0.3216) — an in-silico prediction, not a clinical call.

DDC p.Ala225Asp

c.674C>A · rs141265809 · VCV2316423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3216 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3216	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -11.95	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 2	GERP 0.77, phastCons 0.95
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	23.1	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 0.000169% European (non-Finnish) · 2/1,180,054 alleles

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

Overall 0.000124% 2/1,613,658 alleles · very rare exomes 2/1,461,444 · genomes 0/152,214 · 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.Ala225Asp
Coding: c.674C>A
MANE Select: NM_001082971
dbSNP: rs141265809
Type: single nucleotide variant
Location: chr7:50528177 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 225: an α-helix

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

Similar variants

DDC p.Ala225Val Uncertain significance ★ ⚠ same residue
DDC p.Arg285Gln Uncertain significance ★★ ⚠ same condition
DDC p.Arg379His Uncertain significance ★★ ⚠ same condition
DDC p.Arg393Gly Uncertain significance ★★ ⚠ same condition
DDC p.Arg397His Uncertain significance ★★ ⚠ same condition
DDC p.Arg426Lys Uncertain significance ★★ ⚠ same condition
DDC p.Arg453His Uncertain significance ★★ ⚠ same condition
DDC p.Thr152Asn Uncertain significance ★★ 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-ala225asp (accessed [today's date]).

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