Is DMWD p.Pro454= (c.1362C>G) pathogenic?

DMWD p.Pro454= (c.1362C>G) is classified Benign in DMWD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-29). Common (popmax 94.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DMWD-related disorder.

What condition is associated with DMWD p.Pro454= (c.1362C>G)?

DMWD p.Pro454= (c.1362C>G) is associated with DMWD-related disorder (ClinVar).

DMWD p.Pro454=

Q: How common is DMWD p.Pro454= (c.1362C>G) in the general population?

DMWD p.Pro454= (c.1362C>G) is common (popmax 94.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1362C>G · rs8110017 · VCV3058897

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 94.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DMWD-related disorder

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 -16	GERP -3.6
Overall
CADD	0.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.9% African / African-American · 69,818/73,568 alleles

Filtering AF 94.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 94.1%

Overall 83.7% 1,294,144/1,545,796 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	94.9%	1
Admixed American	89.5%	1
East Asian	89.4%	1
South Asian	88.3%	1
Middle Eastern	86.4%	1
Remaining individualsnot grpmax-eligible	84.5%	1
European (non-Finnish)	82.5%	1
Ashkenazi Jewishnot grpmax-eligible	80.9%	1
Finnishnot grpmax-eligible	78.2%	1
Amishnot grpmax-eligible	60.8%	2

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: DMWD
Protein: p.Pro454=
Coding: c.1362C>G
MANE Select: NM_004943
dbSNP: rs8110017
Type: single nucleotide variant
Location: chr19:45786134 (GRCh38)
Gene constraint: LOEUF 0.65 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 69.73

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

Disease context

DMWD-related disorder

Similar variants

DMWD p.Pro454Leu Uncertain significance ★ ⚠ same residue
DMWD p.Ala109= Benign same condition
DMWD p.Ala472= Benign same condition
DMWD p.Ala582Val Benign same condition
DMWD p.Gly120= Benign same condition
DMWD p.Gly415= Benign same condition
DMWD p.Pro294= Benign same condition
DMWD p.Pro417= Benign 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/dmwd-p-pro454 (accessed [today's date]).

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