Is MPEG1 p.Val394Ile (c.1180G>A) pathogenic?

MPEG1 p.Val394Ile (c.1180G>A) is classified Likely benign in MPEG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-27). AlphaMissense: likely benign (0.0678); Very rare (popmax 0.00133%, afr); Associated with immunodeficiency 77.

What condition is associated with MPEG1 p.Val394Ile (c.1180G>A)?

MPEG1 p.Val394Ile (c.1180G>A) is associated with immunodeficiency 77 (ClinVar).

How common is MPEG1 p.Val394Ile (c.1180G>A) in the general population?

MPEG1 p.Val394Ile (c.1180G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about MPEG1 p.Val394Ile (c.1180G>A)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

MPEG1 p.Val394Ile

c.1180G>A · VCV4852263

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 77

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.81	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 -0.35	GERP -3
Regional constraint	o/e 1.00	unconstrained · MANE · 2,147 bp · p 0.89 · regional, not allelic
Overall
CADD	6.808	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 0.00133% African / African-American · 1/74,928 alleles

Overall 0.000124% 2/1,614,082 alleles · very rare exomes 1/1,461,892 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
European (non-Finnish)	8.47e-05%	1,180,048

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: MPEG1
Protein: p.Val394Ile
Coding: c.1180G>A
MANE Select: NM_001039396
Type: single nucleotide variant
Location: chr11:59211686 (GRCh38)
Gene constraint: LOEUF 1.941 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 5 PDB
Residue 394: a β-strand

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-val394ile (accessed [today's date]).

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