Is MPG p.Ile155Phe (c.463A>T) pathogenic?

MPG p.Ile155Phe (c.463A>T) is classified Uncertain significance in MPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1264); Very rare (popmax 0.000932%, nfe).

How common is MPG p.Ile155Phe (c.463A>T) in the general population?

MPG p.Ile155Phe (c.463A>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about MPG p.Ile155Phe (c.463A>T)?

AlphaMissense predicts likely benign (score 0.1264) — an in-silico prediction, not a clinical call.

MPG p.Ile155Phe

c.463A>T · VCV4836771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1264	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -4.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.1
Regional constraint	o/e 1.10	unconstrained · MANE · 7,464 bp · p 0.053 · regional, not allelic
Overall
CADD	0.387	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I160F vs ClinVar I155F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,878 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,074 alleles · very rare exomes 11/1,460,760 · genomes 0/152,314 · joint denominator

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: MPG
Protein: p.Ile155Phe
Coding: c.463A>T
MANE Select: NM_001015052
Type: single nucleotide variant
Location: chr16:83214 (GRCh38)
Gene constraint: LOEUF 1.468 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.08 · 9 PDB
Residue 160 UniProt numbering: a β-strand

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

Similar variants

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
MPG p.Arg105Gln 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-ile155phe (accessed [today's date]).

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