Is DPM1 p.Thr223= (c.669T>C) pathogenic?

DPM1 p.Thr223= (c.669T>C) is classified Likely benign in DPM1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-07-01). Ultra-rare (popmax 0.0267%, amr); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Thr223= (c.669T>C)?

DPM1 p.Thr223= (c.669T>C) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Thr223= (c.669T>C) in the general population?

DPM1 p.Thr223= (c.669T>C) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

How is DPM1-CDG inherited?

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

DPM1 p.Thr223=

c.669T>C · rs561078570 · VCV728418

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.017	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.26	GERP -2.6
Overall
CADD	6.609	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,020 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.000993% 16/1,610,736 alleles · ultra-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.Thr223=
Coding: c.669T>C
dbSNP: rs561078570
Type: single nucleotide variant
Location: chr20:50936157 (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-thr223 (accessed [today's date]).

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