Is MPC1 p.Pro37Ser (c.109C>T) pathogenic?

MPC1 p.Pro37Ser (c.109C>T) is classified Likely pathogenic in MPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-02). AlphaMissense: likely pathogenic (0.978); Absent from gnomAD v4.1; Associated with mitochondrial pyruvate carrier deficiency.

What condition is associated with MPC1 p.Pro37Ser (c.109C>T)?

MPC1 p.Pro37Ser (c.109C>T) is associated with mitochondrial pyruvate carrier deficiency (ClinVar).

How common is MPC1 p.Pro37Ser (c.109C>T) in the general population?

MPC1 p.Pro37Ser (c.109C>T) is absent from gnomAD v4.1 (gnomAD).

How is Mitochondrial pyruvate carrier deficiency inherited?

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

What do computational predictors say about MPC1 p.Pro37Ser (c.109C>T)?

AlphaMissense predicts likely pathogenic (score 0.978) — an in-silico prediction, not a clinical call.

MPC1 p.Pro37Ser

c.109C>T · rs2114943862 · VCV1299296

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mitochondrial pyruvate carrier deficiency

Computational evidence

Protein change
AlphaMissense	0.978	likely pathogenic ✓ concordant with ClinVar
REVEL	0.607	indeterminate
SaProt	LLR -12.54	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP -0.67, phastCons 1
Regional constraint	o/e 0.15	constrained · MANE · 48 bp · p 0.0001 · regional, not allelic
Overall
CADD	26.8	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

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: MPC1
Protein: p.Pro37Ser
Coding: c.109C>T
MANE Select: NM_016098
dbSNP: rs2114943862
Type: single nucleotide variant
Location: chr6:166366858 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 92.85 · 13 PDB
Residue 37: an α-helix

Full MPC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial pyruvate carrier deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mitochondrial pyruvate carrier deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

MPC1 p.Ala70Thr Likely pathogenic ★ same condition
MPC1 p.Arg97Gln Likely pathogenic ★ same condition
MPC1 p.Arg97Trp Pathogenic ★ same condition
MPC1 p.Lys72Glu Likely pathogenic ★ same condition
MPC1 p.Gln74Lys Uncertain significance ★ ⚠ same condition
MPC1 p.Leu92Val Uncertain significance ★ ⚠ same condition
MPC1 p.Leu79His Pathogenic same condition
MPC1 p.Arg76Gln Uncertain significance ★★ ⚠ same type

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/mpc1-p-pro37ser (accessed [today's date]).

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