Is DPM1 p.Ser248Pro (c.742T>C) pathogenic?

DPM1 p.Ser248Pro (c.742T>C) is classified Likely pathogenic in DPM1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-11-01). AlphaMissense: likely pathogenic (0.7711); Very rare (popmax 0.00034%, nfe); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Ser248Pro (c.742T>C)?

DPM1 p.Ser248Pro (c.742T>C) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Ser248Pro (c.742T>C) in the general population?

DPM1 p.Ser248Pro (c.742T>C) is very rare (popmax 0.00034%, nfe) (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.Ser248Pro (c.742T>C)?

AlphaMissense predicts likely pathogenic (score 0.7711) — an in-silico prediction, not a clinical call.

DPM1 p.Ser248Pro

c.742T>C · rs587777114 · VCV100634

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
AlphaMissense	0.7711	likely pathogenic ✓ concordant with ClinVar
REVEL	0.651	pathogenic-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,080 bp · p 0.94 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,175,730 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000275% 4/1,456,680 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.Ser248Pro
Coding: c.742T>C
dbSNP: rs587777114
Type: single nucleotide variant
Location: chr20:50935173 (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-ser248pro (accessed [today's date]).

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