Is DMWD p.Pro53Arg (c.158C>G) pathogenic?

DMWD p.Pro53Arg (c.158C>G) is classified Uncertain significance in DMWD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-15). AlphaMissense: likely benign (0.1346); Absent from gnomAD v4.1.

How common is DMWD p.Pro53Arg (c.158C>G) in the general population?

DMWD p.Pro53Arg (c.158C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMWD p.Pro53Arg (c.158C>G)?

AlphaMissense predicts likely benign (score 0.1346) — an in-silico prediction, not a clinical call.

DMWD p.Pro53Arg

c.158C>G · VCV3840597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1346 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1346	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 257 bp · p 0.043 · regional, not allelic
Overall
CADD	23.2	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

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.Pro53Arg
Coding: c.158C>G
MANE Select: NM_004943
Type: single nucleotide variant
Location: chr19:45792599 (GRCh38)
Gene constraint: LOEUF 0.65 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 69.73
Residue 53: the 'disordered' region

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

Similar variants

DMWD p.Pro53Ala Uncertain significance ★ ⚠ same residue
DMWD p.Pro53Leu 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

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-pro53arg (accessed [today's date]).

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