Is MPG p.Pro20Leu (c.59C>T) pathogenic?

MPG p.Pro20Leu (c.59C>T) is classified Likely benign in MPG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0724); Absent from gnomAD v4.1.

How common is MPG p.Pro20Leu (c.59C>T) in the general population?

MPG p.Pro20Leu (c.59C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPG p.Pro20Leu (c.59C>T)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

MPG p.Pro20Leu

c.59C>T · rs2542772270 · VCV3201801

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.8
Regional constraint	o/e 1.10	unconstrained · MANE · 7,464 bp · p 0.053 · regional, not allelic
Overall
CADD	0.098	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P25L vs ClinVar P20L) — verify the residue.

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: MPG
Protein: p.Pro20Leu
Coding: c.59C>T
MANE Select: NM_001015052
dbSNP: rs2542772270
Type: single nucleotide variant
Location: chr16:79459 (GRCh38)
Gene constraint: LOEUF 1.468 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.08 · 9 PDB
Residue 25 UniProt numbering: the 'disordered' region

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

Similar variants

MPG p.Pro20Ala Uncertain significance ★ ⚠ same residue
MPG p.Val280Ile Uncertain significance ★★ ⚠ same type
MPG p.Ala200Thr Uncertain significance ★ ⚠ same type
MPG p.Ala21Pro Uncertain significance ★ ⚠ same type
MPG p.Ala221Ser Uncertain significance ★ ⚠ same type
MPG p.Ala255Val Uncertain significance ★ ⚠ same type
MPG p.Ala96Glu Uncertain significance ★ ⚠ same type
MPG p.Arg104Gln 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/mpg-p-pro20leu (accessed [today's date]).

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