Is MPI p.Phe160Cys (c.479T>G) pathogenic?

MPI p.Phe160Cys (c.479T>G) is classified Uncertain significance in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.3664); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with MPI p.Phe160Cys (c.479T>G)?

MPI p.Phe160Cys (c.479T>G) is associated with Inborn genetic diseases (ClinVar).

How common is MPI p.Phe160Cys (c.479T>G) in the general population?

MPI p.Phe160Cys (c.479T>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MPI p.Phe160Cys (c.479T>G)?

AlphaMissense predicts ambiguous (score 0.3664) — an in-silico prediction, not a clinical call.

MPI p.Phe160Cys

c.479T>G · VCV4828266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3664	ambiguous
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -10.13	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,032 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,888 alleles · very rare

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: MPI
Protein: p.Phe160Cys
Coding: c.479T>G
MANE Select: NM_002435
Type: single nucleotide variant
Location: chr15:74892794 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPI p.Asn273Ser Uncertain significance ★★ ⚠ same condition
MPI p.Asp80Asn Uncertain significance ★★ ⚠ same condition
MPI p.Glu331Ala Uncertain significance ★★ ⚠ same condition
MPI p.Lys360Arg Uncertain significance ★★ ⚠ same condition
MPI p.Pro326Ser Uncertain significance ★★ ⚠ same condition
MPI p.Thr177Ile Uncertain significance ★★ ⚠ same condition
MPI p.Val158Ile Uncertain significance ★★ ⚠ same condition
MPI p.Val210Met Uncertain significance ★★ ⚠ same condition

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/mpi-p-phe160cys (accessed [today's date]).

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