MECOM p.Ser962=
c.2886T>C · VCV3684232
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0231%, sas)
Conditions
1
Inborn genetic diseases
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 -0.001 | GERP -4.6, phastCons 0.086 |
| Overall | ||
| CADD | 3.668 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0231%
South Asian · 21/90,832 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.013%
Overall
0.00149%
24/1,613,258 alleles · ultra-rare
exomes 24/1,460,892 · genomes 0/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0231% | 4,325 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
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.Ser962=
- Coding
- c.2886T>C
- MANE Select
- NM_004991
- Type
- single nucleotide variant
- Location
- chr3:169095209 (GRCh38)
- Gene constraint
- LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.04 · 1 PDB
Similar variants
- MECOM p.Ala1022Gly Uncertain significance ★★ ⚠ same condition
- MECOM p.Ala1228Val Uncertain significance ★★ ⚠ same condition
- MECOM p.Ala222Val Uncertain significance ★★ ⚠ same condition
- MECOM p.Ala434Val Uncertain significance ★★ ⚠ same condition
- MECOM p.Ala477Gly Uncertain significance ★★ ⚠ same condition
- MECOM p.Ala537Thr Uncertain significance ★★ ⚠ same condition
- MECOM p.Ala653Val Uncertain significance ★★ ⚠ same condition
- MECOM p.Ala688Asp 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/mecom-p-ser962 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown