Is DPM1 p.Ala2Pro (c.4G>C) pathogenic?

DPM1 p.Ala2Pro (c.4G>C) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.0982); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with DPM1 p.Ala2Pro (c.4G>C)?

DPM1 p.Ala2Pro (c.4G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DPM1 p.Ala2Pro (c.4G>C) in the general population?

DPM1 p.Ala2Pro (c.4G>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about DPM1 p.Ala2Pro (c.4G>C)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

DPM1 p.Ala2Pro

c.4G>C · VCV4617932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -7.76	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 4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.19 · regional, not allelic
Overall
CADD	21.9	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 6.84e-05%

Overall 6.84e-05% 1/1,461,476 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: DPM1
Protein: p.Ala2Pro
Coding: c.4G>C
MANE Select: NM_003859
Type: single nucleotide variant
Location: chr20:50958520 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.61
Residue 2: a modified residue (n-acetylalanine)

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

Similar variants

DPM1 p.Ala2Val Uncertain significance ★ ⚠ same residue
DPM1 p.Ala2= Likely benign ★ same residue
DPM1 p.Arg12Met Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg191Gln Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg20Leu Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg216Gln Uncertain significance ★★ same condition
DPM1 p.Glu193Asp Uncertain significance ★★ ⚠ same condition
DPM1 p.Glu79Gln Uncertain significance ★★ ⚠ same condition

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-ala2pro (accessed [today's date]).

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