Is MPC1 p.Arg97Trp (c.289C>T) pathogenic?

MPC1 p.Arg97Trp (c.289C>T) is classified Pathogenic in MPC1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-14). AlphaMissense: likely pathogenic (0.9388); Very rare (popmax 0.000509%, nfe); Associated with mitochondrial pyruvate carrier deficiency.

What condition is associated with MPC1 p.Arg97Trp (c.289C>T)?

MPC1 p.Arg97Trp (c.289C>T) is associated with mitochondrial pyruvate carrier deficiency (ClinVar).

How common is MPC1 p.Arg97Trp (c.289C>T) in the general population?

MPC1 p.Arg97Trp (c.289C>T) is very rare (popmax 0.000509%, nfe) (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.Arg97Trp (c.289C>T)?

AlphaMissense predicts likely pathogenic (score 0.9388) — an in-silico prediction, not a clinical call.

MPC1 p.Arg97Trp

c.289C>T · rs387907237 · VCV35561

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial pyruvate carrier deficiency

Computational evidence

Protein change
AlphaMissense	0.9388	likely pathogenic ✓ concordant with ClinVar
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -15.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.25	donor loss, 16 bp away · masked 0 · deltas
Pangolin	Δ0.33	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.4	GERP -0.83, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,410 bp · p 0.063 · regional, not allelic
Overall
CADD	31.0	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 0.000509% European (non-Finnish) · 6/1,179,186 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,612,856 alleles · very rare exomes 7/1,460,708 · genomes 0/152,148 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,972
European (non-Finnish)grpmax	0.000509%	196,531

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MPC1
Protein: p.Arg97Trp
Coding: c.289C>T
MANE Select: NM_016098
dbSNP: rs387907237
Type: single nucleotide variant
Location: chr6:166365990 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 92.85 · 13 PDB
Residue 97: a UniProt-annotated variant site (in mpycd; inactive); 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.Arg97Gln Likely pathogenic ★ same residue
MPC1 p.Ala70Thr Likely 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.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-arg97trp (accessed [today's date]).

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