Is DMWD p.Arg44Ser (c.132G>C) pathogenic?

DMWD p.Arg44Ser (c.132G>C) is classified Uncertain significance in DMWD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: ambiguous (0.4536); Ultra-rare (popmax 0.0681%, amr).

How common is DMWD p.Arg44Ser (c.132G>C) in the general population?

DMWD p.Arg44Ser (c.132G>C) is ultra-rare (popmax 0.0681%, amr) (gnomAD).

What do computational predictors say about DMWD p.Arg44Ser (c.132G>C)?

AlphaMissense predicts ambiguous (score 0.4536) — an in-silico prediction, not a clinical call.

DMWD p.Arg44Ser

c.132G>C · rs947962433 · VCV3083188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4536 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4536	ambiguous
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.42	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.41	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.88	GERP -2.2, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 257 bp · p 0.043 · regional, not allelic
Overall
CADD	19.89	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

Grpmax group 0.0681% Admixed American · 26/38,192 alleles

Filtering AF 0.0476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0409%

Overall 0.0042% 56/1,333,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
Admixed Americangrpmax	0.0681%	1,469
African / African-American	0.00307%	32,581
European (non-Finnish)	0.00253%	39,460
Remaining individualsnot grpmax-eligible	0.0021%	47,538

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg44Ser
Coding: c.132G>C
MANE Select: NM_004943
dbSNP: rs947962433
Type: single nucleotide variant
Location: chr19:45792625 (GRCh38)
Gene constraint: LOEUF 0.65 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 69.73
Residue 44: the 'disordered' region

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.Ala15Pro 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

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-arg44ser (accessed [today's date]).

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