MECOM p.Arg425=
c.1275G>A · rs35594969 · VCV2017586
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.25%, mid)
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 5 | GERP 2.6, phastCons 1 |
| Overall | ||
| CADD | 12.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.25%
Middle Eastern · 197/6,062 alleles
Filtering AF
2.93%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.89%
Overall
2.06%
33,235/1,614,180 alleles · low-frequency
exomes 31,017/1,461,874 · genomes 2,218/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 3.25% | 31 |
| South Asian | 3.02% | 33 |
| European (non-Finnish) | 2.31% | 43 |
| Remaining individualsnot grpmax-eligible | 1.95% | 51 |
| Ashkenazi Jewishnot grpmax-eligible | 1.66% | 60 |
| Admixed American | 0.933% | 107 |
| Finnishnot grpmax-eligible | 0.787% | 127 |
| African / African-American | 0.331% | 303 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| East Asian | 0.00891% | 11,223 |
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.Arg425=
- Coding
- c.1275G>A
- MANE Select
- NM_004991
- dbSNP
- rs35594969
- Type
- single nucleotide variant
- Location
- chr3:169116597 (GRCh38)
- Gene constraint
- LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.04 · 1 PDB
- Residue 425
- the 'interaction with mapk9, smad3 and probably suv39h1' region
Similar variants
- MECOM p.Arg425Lys Uncertain significance ★ ⚠ same residue
- MECOM p.Arg425del 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
- MECOM p.Ala1022Gly 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-arg425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown