Is DPM1 p.Asp158Glu (c.474T>A) pathogenic?

DPM1 p.Asp158Glu (c.474T>A) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.7945); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DPM1 p.Asp158Glu (c.474T>A)?

DPM1 p.Asp158Glu (c.474T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPM1 p.Asp158Glu (c.474T>A) in the general population?

DPM1 p.Asp158Glu (c.474T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPM1 p.Asp158Glu (c.474T>A)?

AlphaMissense predicts likely pathogenic (score 0.7945) — an in-silico prediction, not a clinical call.

DPM1 p.Asp158Glu

c.474T>A · rs778874453 · VCV2296246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7945	likely pathogenic
REVEL	0.687	pathogenic-leaning
SaProt	LLR -12.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.1	GERP -0.68, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 5,851 bp · p 0.0004 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: DPM1
Protein: p.Asp158Glu
Coding: c.474T>A
dbSNP: rs778874453
Type: single nucleotide variant
Location: chr20:50942051 (GRCh38)

Full DPM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/dpm1-p-asp158glu (accessed [today's date]).

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