Is DMWD p.Ala15Pro (c.43G>C) pathogenic?

DMWD p.Ala15Pro (c.43G>C) is classified Uncertain significance in DMWD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0995); Ultra-rare (popmax 0.0237%, mid).

How common is DMWD p.Ala15Pro (c.43G>C) in the general population?

DMWD p.Ala15Pro (c.43G>C) is ultra-rare (popmax 0.0237%, mid) (gnomAD).

What do computational predictors say about DMWD p.Ala15Pro (c.43G>C)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

DMWD p.Ala15Pro

c.43G>C · rs1326070828 · VCV3083196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -0.12, phastCons 0.99
Regional constraint	o/e 1.18	unconstrained · MANE · 257 bp · p 0.043 · regional, not allelic
Overall
CADD	19.84	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

Grpmax group 0.0237% Middle Eastern · 1/4,222 alleles

Filtering AF 0.00117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000965%

Overall 0.00172% 21/1,218,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0237%	4,222
Admixed American	0.00321%	31,188
Remaining individualsnot grpmax-eligible	0.00236%	42,442
European (non-Finnish)	0.00187%	53,450

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.Ala15Pro
Coding: c.43G>C
MANE Select: NM_004943
dbSNP: rs1326070828
Type: single nucleotide variant
Location: chr19:45792714 (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

Similar variants

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.Ala20Thr Uncertain significance ★ ⚠ same type
DMWD p.Ala250Thr Uncertain significance ★ ⚠ same type
DMWD p.Ala2Pro Uncertain significance ★ ⚠ same type
DMWD p.Ala3Val 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-ala15pro (accessed [today's date]).

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