Is MPC1 p.Met67Val (c.199A>G) pathogenic?

MPC1 p.Met67Val (c.199A>G) is classified Uncertain significance in MPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.746); Absent from gnomAD v4.1.

How common is MPC1 p.Met67Val (c.199A>G) in the general population?

MPC1 p.Met67Val (c.199A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPC1 p.Met67Val (c.199A>G)?

AlphaMissense predicts likely pathogenic (score 0.746) — an in-silico prediction, not a clinical call.

MPC1 p.Met67Val

c.199A>G · VCV4109728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.746 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.746	likely pathogenic
REVEL	0.654	pathogenic-leaning
SaProt	LLR -13.86	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,410 bp · p 0.063 · regional, not allelic
Overall
CADD	25.8	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

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.Met67Val
Coding: c.199A>G
MANE Select: NM_016098
Type: single nucleotide variant
Location: chr6:166366080 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 92.85 · 13 PDB
Residue 67: an α-helix

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

Similar variants

MPC1 p.Arg76Gln Uncertain significance ★★ ⚠ same type
MPC1 p.Glu102Lys Uncertain significance ★★ ⚠ same type
MPC1 p.Thr106Met Uncertain significance ★★ ⚠ same type
MPC1 c.72-8C>T Likely benign ★★ same type
MPC1 p.Ala10= Benign/Likely benign ★★ same type
MPC1 p.His101= Benign ★★ same type
MPC1 p.Leu36Ile Benign ★★ same type
MPC1 p.Ala70Thr Likely pathogenic ★ 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-met67val (accessed [today's date]).

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