MID1 p.Thr449=
c.1347G>A · rs374960502 · VCV2714753
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0393%, amr)
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 -5.4 | GERP -3.9 |
| Overall | ||
| CADD | 0.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0393%
Admixed American · 18/45,839 alleles
Filtering AF
0.0253%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.00339%
41/1,209,241 alleles · ultra-rare
exomes 27/1,097,139 · genomes 14/112,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0393% | 2,547 |
| Middle Eastern | 0.023% | 4,339 |
| Remaining individualsnot grpmax-eligible | 0.00841% | 11,897 |
| African / African-American | 0.00524% | 19,084 |
| South Asian | 0.00176% | 56,820 |
| European (non-Finnish) | 0.00156% | 63,903 |
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
- MID1
- Protein
- p.Thr449=
- Coding
- c.1347G>A
- MANE Select
- NM_000381
- dbSNP
- rs374960502
- Type
- single nucleotide variant
- Location
- chrX:10459746 (GRCh38)
- Structure
- AlphaFold pLDDT 86.51 · 5 PDB
- Residue 449
- the fibronectin type-iii domain
Similar variants
- MID1 p.Thr449Met Benign ★ ⚠ same residue
- MID1 p.Ala130Thr Pathogenic/Likely pathogenic ★★ same type
- MID1 p.Arg277Ter Pathogenic ★★ same type
- MID1 p.Arg368Ter Pathogenic ★★ same type
- MID1 p.Arg495Ter Pathogenic ★★ same type
- MID1 c.864+4T>G Uncertain significance ★★ same type
- MID1 p.Ala114Thr Uncertain significance ★★ ⚠ same type
- MID1 p.Ala211Pro 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/mid1-p-thr449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown