MPEG1 p.Ala499=
c.1497C>T · VCV3770752
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.107%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.8 | GERP -3.1 |
| Overall | ||
| CADD | 0.292 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.107%
European (non-Finnish) · 1,267/1,180,056 alleles
Filtering AF
0.102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.1%
Overall
0.0826%
1,333/1,614,066 alleles · rare
exomes 1,274/1,461,890 · genomes 59/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.107% | 931 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,736 |
| African / African-American | 0.0147% | 6,810 |
| Admixed American | 0.0117% | 8,572 |
| Finnishnot grpmax-eligible | 0.0109% | 9,147 |
| South Asian | 0.00439% | 22,767 |
| East Asian | 0.00223% | 44,900 |
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.Ala499=
- Coding
- c.1497C>T
- MANE Select
- NM_001039396
- Type
- single nucleotide variant
- Location
- chr11:59211369 (GRCh38)
- Gene constraint
- LOEUF 1.941 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 83.22 · 5 PDB
- Residue 499
- a UniProt-annotated variant site (in imd77; decreased defense response to bacterium); the 'p2' region
Similar variants
- MPEG1 p.Ala525Val Uncertain significance ★★ ⚠ same type
- MPEG1 p.Gln259Glu Uncertain significance ★★ ⚠ same type
- MPEG1 p.Gln713Arg Uncertain significance ★★ ⚠ same type
- MPEG1 p.His420Tyr Uncertain significance ★★ ⚠ same type
- MPEG1 p.Ala467= Benign ★★ same type
- MPEG1 p.Thr73Ala Likely benign ★★ same type
- MPEG1 p.Ala238Thr Uncertain significance ★ ⚠ same type
- MPEG1 p.Ala238Val 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/mpeg1-p-ala499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown