Is MPEG1 p.Phe360Ile (c.1078T>A) pathogenic?

MPEG1 p.Phe360Ile (c.1078T>A) is classified Uncertain significance in MPEG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: ambiguous (0.4368); Absent from gnomAD v4.1; Associated with immunodeficiency 77.

What condition is associated with MPEG1 p.Phe360Ile (c.1078T>A)?

MPEG1 p.Phe360Ile (c.1078T>A) is associated with immunodeficiency 77 (ClinVar).

How common is MPEG1 p.Phe360Ile (c.1078T>A) in the general population?

MPEG1 p.Phe360Ile (c.1078T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPEG1 p.Phe360Ile (c.1078T>A)?

AlphaMissense predicts ambiguous (score 0.4368) — an in-silico prediction, not a clinical call.

MPEG1 p.Phe360Ile

c.1078T>A · rs2496452042 · VCV3065892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4368 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency 77

Computational evidence

Protein change
AlphaMissense	0.4368	ambiguous
REVEL	0.457	indeterminate
SaProt	LLR -9.84	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,147 bp · p 0.89 · regional, not allelic
Overall
CADD	26.0	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

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: MPEG1
Protein: p.Phe360Ile
Coding: c.1078T>A
MANE Select: NM_001039396
dbSNP: rs2496452042
Type: single nucleotide variant
Location: chr11:59211788 (GRCh38)
Gene constraint: LOEUF 1.941 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 5 PDB
Residue 360: a functional site (cleavage; by lgmn)

Full MPEG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 77 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPEG1 p.Ala525Val Uncertain significance ★★ ⚠ same condition
MPEG1 p.His420Tyr Uncertain significance ★★ ⚠ same condition
MPEG1 p.Thr73Ala Likely benign ★★ same condition
MPEG1 p.Asn249Ser Uncertain significance ★ ⚠ same condition
MPEG1 p.Asn315= Uncertain significance ★ same condition
MPEG1 p.Gln227Ter Uncertain significance ★ same condition
MPEG1 p.Gly379Val Uncertain significance ★ ⚠ same condition
MPEG1 p.Gly530Glu 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/mpeg1-p-phe360ile (accessed [today's date]).

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