Is MPC2 p.Ala11Pro (c.31G>C) pathogenic?

MPC2 p.Ala11Pro (c.31G>C) is classified Uncertain significance in MPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.6289); Very rare (popmax 0.0071%, sas).

How common is MPC2 p.Ala11Pro (c.31G>C) in the general population?

MPC2 p.Ala11Pro (c.31G>C) is very rare (popmax 0.0071%, sas) (gnomAD).

What do computational predictors say about MPC2 p.Ala11Pro (c.31G>C)?

AlphaMissense predicts likely pathogenic (score 0.6289) — an in-silico prediction, not a clinical call.

MPC2 p.Ala11Pro

c.31G>C · rs761366753 · VCV2290824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0071%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6289	likely pathogenic
REVEL	0.334	indeterminate
SaProt	LLR -13.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.4	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	29.3	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

Grpmax group 0.0071% South Asian · 6/84,518 alleles

Filtering AF 0.00305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000578% 9/1,556,080 alleles · very rare exomes 9/1,403,762 · genomes 0/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0071%	14,086
Remaining individualsnot grpmax-eligible	0.00332%	30,094
European (non-Finnish)	8.69e-05%	1,150,376

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.Ala11Pro
Coding: c.31G>C
MANE Select: NM_001143674
dbSNP: rs761366753
Type: single nucleotide variant
Location: chr1:167935811 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 89.34 · 17 PDB
Residue 11: an α-helix

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

Similar variants

MPC2 p.Ile47Val Uncertain significance ★ ⚠ same type
MPC2 p.Leu111Val Uncertain significance ★ ⚠ same type
MPC2 p.Leu31Ser Uncertain significance ★ ⚠ same type
MPC2 p.Lys27Arg Uncertain significance ★ ⚠ same type
MPC2 p.Met76Thr Uncertain significance ★ ⚠ same type
MPC2 p.Ser68Arg Uncertain significance ★ ⚠ same type
MPC2 p.Ser86Leu Uncertain significance ★ ⚠ same type
MPC2 p.Thr12Ala 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/mpc2-p-ala11pro (accessed [today's date]).

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