Is DTWD1 p.Cys194Phe (c.581G>T) pathogenic?

DTWD1 p.Cys194Phe (c.581G>T) is classified Uncertain significance in DTWD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.0684); Absent from gnomAD v4.1.

How common is DTWD1 p.Cys194Phe (c.581G>T) in the general population?

DTWD1 p.Cys194Phe (c.581G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DTWD1 p.Cys194Phe (c.581G>T)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

DTWD1 p.Cys194Phe

c.581G>T · VCV3273960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.81	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 -0.019	GERP 0.024
Regional constraint	o/e 0.98	unconstrained · MANE · 18 kb · p 0.72 · regional, not allelic
Overall
CADD	10.45	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DTWD1
Protein: p.Cys194Phe
Coding: c.581G>T
MANE Select: NM_001144955
Type: single nucleotide variant
Location: chr15:49634708 (GRCh38)
Gene constraint: LOEUF 1.283 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50

Full DTWD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTWD1 p.Ala31Ser Uncertain significance ★ ⚠ same type
DTWD1 p.Arg178Cys Uncertain significance ★ ⚠ same type
DTWD1 p.Arg178His Uncertain significance ★ ⚠ same type
DTWD1 p.Arg238His Uncertain significance ★ ⚠ same type
DTWD1 p.Asn210Ser Uncertain significance ★ ⚠ same type
DTWD1 p.Asn78His Uncertain significance ★ ⚠ same type
DTWD1 p.Asp188Val Uncertain significance ★ ⚠ same type
DTWD1 p.Asp275Asn 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/dtwd1-p-cys194phe (accessed [today's date]).

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