MACF1 p.Pro4773=
c.14319T>A · rs143338205 · VCV2045376
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.145%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.075 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.055 | GERP -3, phastCons 0.54 |
| Overall | ||
| CADD | 4.885 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.145%
Admixed American · 87/59,856 alleles
Filtering AF
0.121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.112%
Overall
0.0991%
1,597/1,611,888 alleles · rare
exomes 1,476/1,459,692 · genomes 121/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.145% | 688 |
| European (non-Finnish) | 0.113% | 882 |
| Remaining individualsnot grpmax-eligible | 0.112% | 891 |
| Finnishnot grpmax-eligible | 0.108% | 926 |
| Middle Eastern | 0.0661% | 1,513 |
| African / African-American | 0.02% | 4,999 |
| South Asian | 0.0176% | 5,685 |
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.Pro4773=
- Coding
- c.14319T>A
- MANE Select
- NM_001394062
- dbSNP
- rs143338205
- Type
- single nucleotide variant
- Location
- chr1:39385904 (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-pro4773 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown