MECOM p.Pro331=
c.993T>C · VCV3699313
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000339%, 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 6.2 | GERP -2.6, phastCons 1 |
| Overall | ||
| CADD | 12.88 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,178,370 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,610,850 alleles · very rare
exomes 4/1,458,524 · genomes 0/152,326 · joint denominator
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
- MECOM
- Protein
- p.Pro331=
- Coding
- c.993T>C
- MANE Select
- NM_004991
- Type
- single nucleotide variant
- Location
- chr3:169121195 (GRCh38)
- Gene constraint
- LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.04 · 1 PDB
- Residue 331
- the 'interaction with mapk9, smad3 and probably suv39h1' region
Similar variants
- MECOM p.Pro331Ala Uncertain significance ★ ⚠ same residue
- MECOM p.Pro331Leu Uncertain significance ★ ⚠ same residue
- MECOM p.Pro331Ser Uncertain significance ★ ⚠ same residue
- MECOM p.Arg938Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- MECOM p.Arg938Trp Pathogenic/Likely pathogenic ★★ same type
- MECOM p.Thr944Ile Likely pathogenic ★★ same type
- MECOM c.2577+4A>T Uncertain significance ★★ same type
- MECOM c.3585+3A>G 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/mecom-p-pro331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown