Is MPI p.Phe90Cys (c.269T>G) pathogenic?

MPI p.Phe90Cys (c.269T>G) is classified Uncertain significance in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely pathogenic (0.6658); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPI p.Phe90Cys (c.269T>G)?

MPI p.Phe90Cys (c.269T>G) is associated with Inborn genetic diseases (ClinVar).

How common is MPI p.Phe90Cys (c.269T>G) in the general population?

MPI p.Phe90Cys (c.269T>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about MPI p.Phe90Cys (c.269T>G)?

AlphaMissense predicts likely pathogenic (score 0.6658) — an in-silico prediction, not a clinical call.

MPI p.Phe90Cys

c.269T>G · rs2505813810 · VCV2617874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6658	likely pathogenic
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -10.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	27.3	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 0.000424% European (non-Finnish) · 5/1,180,034 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,894 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.Phe90Cys
Coding: c.269T>G
MANE Select: NM_002435
dbSNP: rs2505813810
Type: single nucleotide variant
Location: chr15:74891503 (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-phe90cys (accessed [today's date]).

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