MACF1 p.Val7100=
c.21300G>A · rs749859918 · VCV2723446
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.214 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.24 | donor gain · deltas |
| Pangolin | Δ0.22 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.56 | GERP -3.7, phastCons 0.99 |
| Overall | ||
| CADD | 11.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,996 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000496%
8/1,614,060 alleles · very rare
exomes 5/1,461,838 · genomes 3/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,999 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00133% | 74,930 |
| European (non-Finnish) | 0.000169% | 590,012 |
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
- MACF1
- Protein
- p.Val7100=
- Coding
- c.21300G>A
- MANE Select
- NM_001394062
- dbSNP
- rs749859918
- Type
- single nucleotide variant
- Location
- chr1:39459189 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
- Residue 7100
- an α-helix; the ef-hand 2 domain
Similar variants
- MACF1 p.Arg7251Pro Likely pathogenic ★★ same type
- MACF1 p.Ala5598Ser Uncertain significance ★★ same type
- MACF1 p.Ala601Pro Uncertain significance ★★ ⚠ same type
- MACF1 p.Arg1196Gln Uncertain significance ★★ ⚠ same type
- MACF1 p.Arg30Gln Uncertain significance ★★ same type
- MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same type
- MACF1 p.Arg4674Cys Uncertain significance ★★ same type
- MACF1 p.Arg5490Gln 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/macf1-p-val7100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown