Is DMWD p.Ser69Phe (c.206C>T) pathogenic?

DMWD p.Ser69Phe (c.206C>T) is classified Uncertain significance in DMWD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.1978); Ultra-rare (popmax 0.0138%, nfe).

How common is DMWD p.Ser69Phe (c.206C>T) in the general population?

DMWD p.Ser69Phe (c.206C>T) is ultra-rare (popmax 0.0138%, nfe) (gnomAD).

What do computational predictors say about DMWD p.Ser69Phe (c.206C>T)?

AlphaMissense predicts likely benign (score 0.1978) — an in-silico prediction, not a clinical call.

DMWD p.Ser69Phe

c.206C>T · VCV3840591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1978 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0138%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1978	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -10.50	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.97, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 257 bp · p 0.043 · regional, not allelic
Overall
CADD	23.0	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 0.0138% European (non-Finnish) · 132/953,074 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0115% 136/1,185,646 alleles · ultra-rare exomes 123/1,036,486 · genomes 13/149,160 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0138%	7,220
Remaining individualsnot grpmax-eligible	0.00492%	20,327
African / African-American	0.00325%	30,796

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.Ser69Phe
Coding: c.206C>T
MANE Select: NM_004943
Type: single nucleotide variant
Location: chr19:45792551 (GRCh38)
Gene constraint: LOEUF 0.65 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 69.73
Residue 69: 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-ser69phe (accessed [today's date]).

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