Is DPM1 p.Ser230Ala (c.688T>G) pathogenic?

DPM1 p.Ser230Ala (c.688T>G) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.145); Absent from gnomAD v4.1; Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Ser230Ala (c.688T>G)?

DPM1 p.Ser230Ala (c.688T>G) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Ser230Ala (c.688T>G) in the general population?

DPM1 p.Ser230Ala (c.688T>G) 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.Ser230Ala (c.688T>G)?

AlphaMissense predicts likely benign (score 0.145) — an in-silico prediction, not a clinical call.

DPM1 p.Ser230Ala

c.688T>G · rs1985042327 · VCV1034691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.145 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
AlphaMissense	0.145	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.59, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,080 bp · p 0.94 · regional, not allelic
Overall
CADD	23.6	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

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.Ser230Ala
Coding: c.688T>G
MANE Select: NM_003859
dbSNP: rs1985042327
Type: single nucleotide variant
Location: chr20:50935227 (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

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

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.Arg20Leu 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-ser230ala (accessed [today's date]).

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