Is DMWD p.Arg458Pro (c.1373G>C) pathogenic?

DMWD p.Arg458Pro (c.1373G>C) is classified Uncertain significance in DMWD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-05). AlphaMissense: ambiguous (0.3415); Absent from gnomAD v4.1.

How common is DMWD p.Arg458Pro (c.1373G>C) in the general population?

DMWD p.Arg458Pro (c.1373G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMWD p.Arg458Pro (c.1373G>C)?

AlphaMissense predicts ambiguous (score 0.3415) — an in-silico prediction, not a clinical call.

DMWD p.Arg458Pro

c.1373G>C · rs767756465 · VCV2258819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3415 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3415	ambiguous
REVEL	0.282	benign-leaning
SaProt	LLR -7.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,913 bp · p 0.1 · regional, not allelic
Overall
CADD	23.7	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: DMWD
Protein: p.Arg458Pro
Coding: c.1373G>C
MANE Select: NM_004943
dbSNP: rs767756465
Type: single nucleotide variant
Location: chr19:45786123 (GRCh38)
Gene constraint: LOEUF 0.65 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 69.73
Residue 458: the 'disordered' region

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

Similar variants

DMWD p.Arg458His Uncertain significance ★ ⚠ same residue
DMWD p.Ala107Ser Uncertain significance ★ ⚠ same type
DMWD p.Ala109Val Uncertain significance ★ ⚠ same type
DMWD p.Ala14Ser Uncertain significance ★ ⚠ same type
DMWD p.Ala14Val Uncertain significance ★ ⚠ same type
DMWD p.Ala15Pro Uncertain significance ★ ⚠ same type
DMWD p.Ala20Thr Uncertain significance ★ ⚠ same type
DMWD p.Ala250Thr 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/dmwd-p-arg458pro (accessed [today's date]).

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