Is DPM1 p.Phe231Ser (c.692T>C) pathogenic?

DPM1 p.Phe231Ser (c.692T>C) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1; Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Phe231Ser (c.692T>C)?

DPM1 p.Phe231Ser (c.692T>C) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Phe231Ser (c.692T>C) in the general population?

DPM1 p.Phe231Ser (c.692T>C) is absent from gnomAD v4.1 (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.Phe231Ser (c.692T>C)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

DPM1 p.Phe231Ser

c.692T>C · rs2123056867 · VCV1497215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic
REVEL	0.766	pathogenic-leaning
SaProt	LLR -17.16	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPM1
Protein: p.Phe231Ser
Coding: c.692T>C
dbSNP: rs2123056867
Type: single nucleotide variant
Location: chr20:50935223 (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-phe231ser (accessed [today's date]).

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