Is MPC1 p.Leu92Val (c.274C>G) pathogenic?

MPC1 p.Leu92Val (c.274C>G) is classified Uncertain significance in MPC1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.1016); Absent from gnomAD v4.1; Associated with mitochondrial pyruvate carrier deficiency.

What condition is associated with MPC1 p.Leu92Val (c.274C>G)?

MPC1 p.Leu92Val (c.274C>G) is associated with mitochondrial pyruvate carrier deficiency (ClinVar).

How common is MPC1 p.Leu92Val (c.274C>G) in the general population?

MPC1 p.Leu92Val (c.274C>G) 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.Leu92Val (c.274C>G)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

MPC1 p.Leu92Val

c.274C>G · rs2534024396 · VCV2627541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mitochondrial pyruvate carrier deficiency

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -9.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.6	GERP -0.56, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,410 bp · p 0.063 · regional, not allelic
Overall
CADD	19.14	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: MPC1
Protein: p.Leu92Val
Coding: c.274C>G
MANE Select: NM_016098
dbSNP: rs2534024396
Type: single nucleotide variant
Location: chr6:166366005 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 92.85 · 13 PDB
Residue 92: 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.Pro37Ser Likely pathogenic ★ same condition
MPC1 p.Gln74Lys 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-leu92val (accessed [today's date]).

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