Is DMWD p.Pro471Ser (c.1411C>T) pathogenic?

DMWD p.Pro471Ser (c.1411C>T) is classified Benign in DMWD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-05). AlphaMissense: likely benign (0.069); Rare (popmax 0.971%, afr); Associated with DMWD-related disorder.

What condition is associated with DMWD p.Pro471Ser (c.1411C>T)?

DMWD p.Pro471Ser (c.1411C>T) is associated with DMWD-related disorder (ClinVar).

How common is DMWD p.Pro471Ser (c.1411C>T) in the general population?

DMWD p.Pro471Ser (c.1411C>T) is rare (popmax 0.971%, afr) (gnomAD).

What do computational predictors say about DMWD p.Pro471Ser (c.1411C>T)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

DMWD p.Pro471Ser

c.1411C>T · rs199536506 · VCV3053155

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.971%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DMWD-related disorder

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.57, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,913 bp · p 0.1 · regional, not allelic
Overall
CADD	18.23	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 0.971% African / African-American · 705/72,584 alleles

Filtering AF 0.912% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.888%

Overall 0.0525% 797/1,518,006 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.971%	103
Admixed American	0.0944%	1,060
Remaining individualsnot grpmax-eligible	0.0684%	1,462
Middle Eastern	0.0176%	5,670
European (non-Finnish)	0.000619%	161,673

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.Pro471Ser
Coding: c.1411C>T
MANE Select: NM_004943
dbSNP: rs199536506
Type: single nucleotide variant
Location: chr19:45786085 (GRCh38)
Gene constraint: LOEUF 0.65 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 69.73
Residue 471: the 'disordered' region

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

Disease context

DMWD-related disorder

Similar variants

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
DMWD p.Pro454= 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-pro471ser (accessed [today's date]).

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