Is MPDU1 p.Ser43Arg (c.127A>C) pathogenic?

MPDU1 p.Ser43Arg (c.127A>C) is classified Uncertain significance in MPDU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.9836); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPDU1 p.Ser43Arg (c.127A>C)?

MPDU1 p.Ser43Arg (c.127A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MPDU1 p.Ser43Arg (c.127A>C) in the general population?

MPDU1 p.Ser43Arg (c.127A>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about MPDU1 p.Ser43Arg (c.127A>C)?

AlphaMissense predicts likely pathogenic (score 0.9836) — an in-silico prediction, not a clinical call.

MPDU1 p.Ser43Arg

c.127A>C · rs764557594 · VCV2324544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9836	likely pathogenic · top 2% in MPDU1
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -17.41	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,685 bp · p 0.29 · regional, not allelic
Overall
CADD	28.8	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

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,998 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,038 alleles · very rare exomes 4/1,461,888 · genomes 0/152,150 · joint denominator

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.Ser43Arg
Coding: c.127A>C
MANE Select: NM_004870
dbSNP: rs764557594
Type: single nucleotide variant
Location: chr17:7585755 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57
Residue 43: the pq-loop 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPDU1 p.Arg200Gln Uncertain significance ★★ ⚠ same condition
MPDU1 p.Thr113Met Uncertain significance ★★ ⚠ same condition
MPDU1 c.169+4T>G Uncertain significance ★ same condition
MPDU1 p.Ala228Thr Uncertain significance ★ ⚠ same condition
MPDU1 p.Ala52Ser Uncertain significance ★ ⚠ same condition
MPDU1 p.Asn161Ser Uncertain significance ★ ⚠ same condition
MPDU1 p.Asp31His Uncertain significance ★ same condition
MPDU1 p.Gln77Pro 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/mpdu1-p-ser43arg (accessed [today's date]).

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