Is MPDU1 p.Ser197Pro (c.589T>C) pathogenic?

MPDU1 p.Ser197Pro (c.589T>C) is classified Uncertain significance in MPDU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely pathogenic (0.9761); No allele count reported in gnomAD v4.1 (AN 1,613,152); Associated with MPDU1-congenital disorder of glycosylation.

What condition is associated with MPDU1 p.Ser197Pro (c.589T>C)?

MPDU1 p.Ser197Pro (c.589T>C) is associated with MPDU1-congenital disorder of glycosylation (ClinVar).

How common is MPDU1 p.Ser197Pro (c.589T>C) in the general population?

MPDU1 p.Ser197Pro (c.589T>C) is no allele count reported in gnomAD v4.1 (AN 1,613,152) (gnomAD).

How is MPDU1-CDG inherited?

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

What do computational predictors say about MPDU1 p.Ser197Pro (c.589T>C)?

AlphaMissense predicts likely pathogenic (score 0.9761) — an in-silico prediction, not a clinical call.

MPDU1 p.Ser197Pro

c.589T>C · rs1213979314 · VCV2052017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9761 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,152)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MPDU1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.9761	likely pathogenic · top 4% in MPDU1
REVEL	0.894	moderately pathogenic-leaning
SaProt	LLR -15.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,685 bp · p 0.29 · regional, not allelic
Overall
CADD	28.7	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

No allele count reported in gnomAD v4.1 (AN 1,613,152). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MPDU1
Protein: p.Ser197Pro
Coding: c.589T>C
MANE Select: NM_004870
dbSNP: rs1213979314
Type: single nucleotide variant
Location: chr17:7587242 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57
Residue 197: the pq-loop 2 domain

Full MPDU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MPDU1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MPDU1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MPDU1 p.Ser197= Likely benign ★ same residue
MPDU1 p.Ala187Val Uncertain significance ★★ ⚠ same condition
MPDU1 p.Arg200Gln Uncertain significance ★★ ⚠ same condition
MPDU1 p.Ile50Thr Uncertain significance ★★ ⚠ same condition
MPDU1 p.Lys238Arg Uncertain significance ★★ ⚠ same condition
MPDU1 p.Thr113Met Uncertain significance ★★ ⚠ same condition
MPDU1 c.103+19C>T Likely benign ★★ same condition
MPDU1 c.169+14C>T Likely benign ★★ 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/mpdu1-p-ser197pro (accessed [today's date]).

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