Is DDN p.Pro246= (c.738C>G) pathogenic?

DDN p.Pro246= (c.738C>G) is classified Likely benign in DDN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Absent from gnomAD v4.1.

How common is DDN p.Pro246= (c.738C>G) in the general population?

DDN p.Pro246= (c.738C>G) is absent from gnomAD v4.1 (gnomAD).

DDN p.Pro246=

c.738C>G · rs2498960970 · VCV2642930

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -3.8
Overall
CADD	0.534	PHRED · no single calibrated threshold — expert panels disagree

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: DDN
Protein: p.Pro246=
Coding: c.738C>G
MANE Select: NM_015086
dbSNP: rs2498960970
Type: single nucleotide variant
Location: chr12:48998138 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 46.28
Residue 246: the 'disordered' region

Full DDN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDN p.Glu661Gly Benign ★★ same type
DDN p.Pro358Arg Benign ★★ same type
DDN p.Ala154Thr Uncertain significance ★ ⚠ same type
DDN p.Ala169Val Uncertain significance ★ ⚠ same type
DDN p.Ala174Glu Uncertain significance ★ ⚠ same type
DDN p.Ala179Thr Uncertain significance ★ ⚠ same type
DDN p.Ala305Thr Uncertain significance ★ ⚠ same type
DDN p.Ala341Thr Uncertain significance ★ ⚠ same type

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/ddn-p-pro246 (accessed [today's date]).

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