Is DTWD2 p.Asp28Ala (c.83A>C) pathogenic?

DTWD2 p.Asp28Ala (c.83A>C) is classified Likely benign in DTWD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely benign (0.0669); Very rare (popmax 0.00167%, amr).

How common is DTWD2 p.Asp28Ala (c.83A>C) in the general population?

DTWD2 p.Asp28Ala (c.83A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DTWD2 p.Asp28Ala (c.83A>C)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

DTWD2 p.Asp28Ala

c.83A>C · rs773721117 · VCV2614306

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.37	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 -0.084	GERP -1.4
Regional constraint	o/e 1.35	unconstrained · MANE · 148 kb · p 8.1e-12 · regional, not allelic
Overall
CADD	7.188	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 0.00167% Admixed American · 1/59,716 alleles

Overall 6.87e-05% 1/1,454,770 alleles · very rare

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.Asp28Ala
Coding: c.83A>C
MANE Select: NM_173666
dbSNP: rs773721117
Type: single nucleotide variant
Location: chr5:118988429 (GRCh38)
Gene constraint: LOEUF 1.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.75
Residue 28: the 'disordered' region

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

Similar variants

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
DTWD2 p.Arg109Cys 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-asp28ala (accessed [today's date]).

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