Is DDC p.Pro35Ala (c.103C>G) pathogenic?

DDC p.Pro35Ala (c.103C>G) is classified Uncertain significance in DDC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: ambiguous (0.4151); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DDC p.Pro35Ala (c.103C>G)?

DDC p.Pro35Ala (c.103C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DDC p.Pro35Ala (c.103C>G) in the general population?

DDC p.Pro35Ala (c.103C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDC p.Pro35Ala (c.103C>G)?

AlphaMissense predicts ambiguous (score 0.4151) — an in-silico prediction, not a clinical call.

DDC p.Pro35Ala

c.103C>G · rs762044255 · VCV2540400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4151 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4151	ambiguous
REVEL	0.709	pathogenic-leaning
SaProt	LLR -8.79	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 0.058 · regional, not allelic
Overall
CADD	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DDC
Protein: p.Pro35Ala
Coding: c.103C>G
MANE Select: NM_001082971
dbSNP: rs762044255
Type: single nucleotide variant
Location: chr7:50543983 (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

Similar variants

DDC p.Pro35= Likely benign ★ 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-pro35ala (accessed [today's date]).

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