MACF1 p.Asp2432=
c.7296C>T · VCV3771070
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.16%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.012 | GERP -1.1, phastCons 0.1 |
| Overall | ||
| CADD | 9.249 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.16%
East Asian · 519/44,882 alleles
Filtering AF
1.07%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.04%
Overall
0.0408%
658/1,614,112 alleles · low-frequency
exomes 556/1,461,874 · genomes 102/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.16% | 86 |
| Remaining individualsnot grpmax-eligible | 0.0608% | 1,645 |
| Middle Eastern | 0.033% | 3,031 |
| Finnishnot grpmax-eligible | 0.0219% | 4,573 |
| South Asian | 0.0198% | 5,060 |
| Admixed American | 0.00833% | 12,004 |
| African / African-American | 0.00533% | 18,755 |
| European (non-Finnish) | 0.00483% | 20,702 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
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.Asp2432=
- Coding
- c.7296C>T
- MANE Select
- NM_001394062
- Type
- single nucleotide variant
- Location
- chr1:39333884 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
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-asp2432 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown