Is MPC1 p.Arg97Gln (c.290G>A) pathogenic?

MPC1 p.Arg97Gln (c.290G>A) is classified Likely pathogenic in MPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-02). AlphaMissense: likely pathogenic (0.9122); Very rare (popmax 0.00133%, afr); Associated with mitochondrial pyruvate carrier deficiency.

What condition is associated with MPC1 p.Arg97Gln (c.290G>A)?

MPC1 p.Arg97Gln (c.290G>A) is associated with mitochondrial pyruvate carrier deficiency (ClinVar).

How common is MPC1 p.Arg97Gln (c.290G>A) in the general population?

MPC1 p.Arg97Gln (c.290G>A) is very rare (popmax 0.00133%, afr) (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.Arg97Gln (c.290G>A)?

AlphaMissense predicts likely pathogenic (score 0.9122) — an in-silico prediction, not a clinical call.

MPC1 p.Arg97Gln

c.290G>A · rs1779135449 · VCV1236163

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial pyruvate carrier deficiency

Computational evidence

Protein change
AlphaMissense	0.9122	likely pathogenic ✓ concordant with ClinVar
REVEL	0.753	pathogenic-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 0.39, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,410 bp · p 0.063 · regional, not allelic
Overall
CADD	29.3	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 0.00133% African / African-American · 1/74,968 alleles

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

Overall 0.00031% 5/1,612,948 alleles · very rare exomes 3/1,460,754 · genomes 2/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,968
European (non-Finnish)	0.000339%	294,808

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.Arg97Gln
Coding: c.290G>A
MANE Select: NM_016098
dbSNP: rs1779135449
Type: single nucleotide variant
Location: chr6:166365989 (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.Arg97Trp 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-arg97gln (accessed [today's date]).

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