Is DTWD2 p.Asp50Glu (c.150C>A) pathogenic?

DTWD2 p.Asp50Glu (c.150C>A) is classified Uncertain significance in DTWD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.09); Very rare (popmax 0.00237%, eas).

How common is DTWD2 p.Asp50Glu (c.150C>A) in the general population?

DTWD2 p.Asp50Glu (c.150C>A) is very rare (popmax 0.00237%, eas) (gnomAD).

What do computational predictors say about DTWD2 p.Asp50Glu (c.150C>A)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

DTWD2 p.Asp50Glu

c.150C>A · VCV3842783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.49	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 -0.046	GERP -4.5
Regional constraint	o/e 1.35	unconstrained · MANE · 148 kb · p 8.1e-12 · regional, not allelic
Overall
CADD	0.33	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 0.00237% East Asian · 1/42,206 alleles

Overall 0.000128% 2/1,568,594 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00237%	42,206
European (non-Finnish)	8.62e-05%	1,159,552

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: DTWD2
Protein: p.Asp50Glu
Coding: c.150C>A
MANE Select: NM_173666
Type: single nucleotide variant
Location: chr5:118988362 (GRCh38)
Gene constraint: LOEUF 1.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.75
Residue 50: the 'disordered' region

Full DTWD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTWD2 p.Asp50Gly Uncertain significance ★ ⚠ same residue
DTWD2 p.Ala227Thr Uncertain significance ★ ⚠ same type
DTWD2 p.Ala228Pro Uncertain significance ★ ⚠ same type
DTWD2 p.Ala230Thr Uncertain significance ★ ⚠ same type
DTWD2 p.Ala250Asp Uncertain significance ★ ⚠ same type
DTWD2 p.Ala40Val Uncertain significance ★ ⚠ same type
DTWD2 p.Ala42Ser Uncertain significance ★ ⚠ same type
DTWD2 p.Ala7Ser 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/dtwd2-p-asp50glu (accessed [today's date]).

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