Is MPDU1 p.Ala135Pro (c.403G>C) pathogenic?

MPDU1 p.Ala135Pro (c.403G>C) is classified Benign in MPDU1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-29). AlphaMissense: ambiguous (0.5326); Low-frequency (popmax 4.22%, eas); Associated with MPDU1-congenital disorder of glycosylation.

What condition is associated with MPDU1 p.Ala135Pro (c.403G>C)?

MPDU1 p.Ala135Pro (c.403G>C) is associated with MPDU1-congenital disorder of glycosylation (ClinVar).

How common is MPDU1 p.Ala135Pro (c.403G>C) in the general population?

MPDU1 p.Ala135Pro (c.403G>C) is low-frequency (popmax 4.22%, eas) (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.Ala135Pro (c.403G>C)?

AlphaMissense predicts ambiguous (score 0.5326) — an in-silico prediction, not a clinical call.

MPDU1 p.Ala135Pro

c.403G>C · rs137983973 · VCV95180

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.5326 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.22%, eas)

Conditions

MPDU1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.5326	ambiguous
REVEL	0.503	indeterminate
SaProt	LLR -11.37	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.3, phastCons 0.93
Regional constraint	o/e 0.94	unconstrained · MANE · 3,685 bp · p 0.29 · regional, not allelic
Overall
CADD	17.35	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 4.22% East Asian · 1,892/44,866 alleles

Filtering AF 4.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.99%

Overall 0.164% 2,648/1,613,988 alleles · low-frequency exomes 2,253/1,461,830 · genomes 395/152,158 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	4.22%	24
Remaining individualsnot grpmax-eligible	0.621%	161
South Asian	0.271%	369
African / African-American	0.108%	925
Admixed American	0.0233%	4,287
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00212%	47,201

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: MPDU1
Protein: p.Ala135Pro
Coding: c.403G>C
MANE Select: NM_004870
dbSNP: rs137983973
Type: single nucleotide variant
Location: chr17:7586913 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57

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.Ala135Thr Uncertain significance ★ ⚠ 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-ala135pro (accessed [today's date]).

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