Is MPC2 p.Ile47Val (c.139A>G) pathogenic?

MPC2 p.Ile47Val (c.139A>G) is classified Uncertain significance in MPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-07). AlphaMissense: likely benign (0.0531); Very rare (popmax 0.00727%, amr).

How common is MPC2 p.Ile47Val (c.139A>G) in the general population?

MPC2 p.Ile47Val (c.139A>G) is very rare (popmax 0.00727%, amr) (gnomAD).

What do computational predictors say about MPC2 p.Ile47Val (c.139A>G)?

AlphaMissense predicts likely benign (score 0.0531) — an in-silico prediction, not a clinical call.

MPC2 p.Ile47Val

c.139A>G · VCV3397576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00727%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0531	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.05	GERP -3.6, phastCons 0.42
Regional constraint	o/e 0.80	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	5.743	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

Grpmax group 0.00727% Admixed American · 4/54,990 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00144%

Overall 0.000818% 13/1,589,422 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00727%	13,747
South Asian	0.00232%	43,187
Remaining individualsnot grpmax-eligible	0.00163%	61,356
European (non-Finnish)	0.000513%	195,030

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: MPC2
Protein: p.Ile47Val
Coding: c.139A>G
MANE Select: NM_001143674
Type: single nucleotide variant
Location: chr1:167924508 (GRCh38)

Full MPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/mpc2-p-ile47val (accessed [today's date]).

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