Is DDC p.Arg319Lys (c.956G>A) pathogenic?

DDC p.Arg319Lys (c.956G>A) is classified Uncertain significance in DDC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.1503); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DDC p.Arg319Lys (c.956G>A)?

DDC p.Arg319Lys (c.956G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DDC p.Arg319Lys (c.956G>A) in the general population?

DDC p.Arg319Lys (c.956G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DDC p.Arg319Lys (c.956G>A)?

AlphaMissense predicts likely benign (score 0.1503) — an in-silico prediction, not a clinical call.

DDC p.Arg319Lys

c.956G>A · VCV3500247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1503 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1503	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	22.6	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 0.00167% Admixed American · 1/60,002 alleles

Overall 0.000186% 3/1,613,514 alleles · very rare exomes 0/1,461,362 · genomes 3/152,152 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,442
European (non-Finnish)	8.48e-05%	1,179,888

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.Arg319Lys
Coding: c.956G>A
MANE Select: NM_001082971
Type: single nucleotide variant
Location: chr7:50479852 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB
Residue 319: 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.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
DDC p.Thr454Met 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-arg319lys (accessed [today's date]).

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