Is DPM1 p.Arg20Leu (c.59G>T) pathogenic?

DPM1 p.Arg20Leu (c.59G>T) is classified Uncertain significance in DPM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-04). AlphaMissense: likely benign (0.1005); Very rare (popmax 0.00936%, afr); Associated with Inborn genetic diseases.

What condition is associated with DPM1 p.Arg20Leu (c.59G>T)?

DPM1 p.Arg20Leu (c.59G>T) is associated with Inborn genetic diseases, congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Arg20Leu (c.59G>T) in the general population?

DPM1 p.Arg20Leu (c.59G>T) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about DPM1 p.Arg20Leu (c.59G>T)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

DPM1 p.Arg20Leu

c.59G>T · rs376257244 · VCV464505

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.78	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 0.09	GERP 0.53, phastCons 0.001
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.19 · regional, not allelic
Overall
CADD	18.3	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 0.00936% African / African-American · 7/74,774 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00062% 10/1,613,574 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,682
Admixed American	0.00333%	29,987
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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.Arg20Leu
Coding: c.59G>T
MANE Select: NM_003859
dbSNP: rs376257244
Type: single nucleotide variant
Location: chr20:50958465 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.61

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

Also linked: congenital disorder of glycosylation type 1E

Similar variants

DPM1 p.Arg92Gly Pathogenic ★★ same condition
DPM1 p.His124Arg Likely pathogenic ★★ same condition
DPM1 p.Met1Leu Pathogenic/Likely pathogenic ★★ same condition
DPM1 c.*12T>C Uncertain significance ★★ same condition
DPM1 p.Ala109Val Uncertain significance ★★ same condition
DPM1 p.Arg12Met Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg191Gln Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg216Gln 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-arg20leu (accessed [today's date]).

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