Is DPM1 p.Arg147His (c.440G>A) pathogenic?

DPM1 p.Arg147His (c.440G>A) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: likely pathogenic (0.9906); Very rare (popmax 0.00533%, afr); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Arg147His (c.440G>A)?

DPM1 p.Arg147His (c.440G>A) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Arg147His (c.440G>A) in the general population?

DPM1 p.Arg147His (c.440G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

How is DPM1-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DPM1 p.Arg147His (c.440G>A)?

AlphaMissense predicts likely pathogenic (score 0.9906) — an in-silico prediction, not a clinical call.

DPM1 p.Arg147His

c.440G>A · rs11553483 · VCV2039058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
AlphaMissense	0.9906	likely pathogenic
REVEL	0.505	indeterminate
SaProt	LLR -14.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.19 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00533% African / African-American · 4/75,058 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000958% 14/1,461,800 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,765
Finnishnot grpmax-eligible	0.00156%	63,994
South Asian	0.0011%	91,080
European (non-Finnish)	0.000678%	147,500

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.Arg147His
Coding: c.440G>A
dbSNP: rs11553483
Type: single nucleotide variant
Location: chr20:50942085 (GRCh38)

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

Disease context

congenital disorder of glycosylation type 1E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DPM1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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-arg147his (accessed [today's date]).

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