MACF1 p.Ala4782=
c.14346C>T · VCV3352883
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.332%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.99 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -4.5, phastCons 0.001 |
| Overall | ||
| CADD | 3.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.332%
Middle Eastern · 20/6,018 alleles
Filtering AF
0.22%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.184%
Overall
0.0285%
459/1,608,988 alleles · rare
exomes 421/1,456,860 · genomes 38/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.332% | 301 |
| South Asian | 0.153% | 656 |
| Remaining individualsnot grpmax-eligible | 0.0289% | 3,457 |
| European (non-Finnish) | 0.0223% | 4,478 |
| Finnishnot grpmax-eligible | 0.0219% | 4,567 |
| Admixed American | 0.00678% | 14,754 |
| African / African-American | 0.00268% | 37,262 |
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.Ala4782=
- Coding
- c.14346C>T
- MANE Select
- NM_001394062
- Type
- single nucleotide variant
- Location
- chr1:39387188 (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-ala4782 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown