MACF1 p.Pro3769=
c.11307A>C · rs148218605 · VCV2064945
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.228%, 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 2.7 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 3.969 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.228%
Admixed American · 137/60,018 alleles
Filtering AF
0.197%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.185%
Overall
0.0384%
620/1,614,140 alleles · rare
exomes 551/1,461,850 · genomes 69/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.228% | 438 |
| Remaining individualsnot grpmax-eligible | 0.0512% | 1,953 |
| European (non-Finnish) | 0.0378% | 2,646 |
| African / African-American | 0.004% | 25,016 |
| Finnishnot grpmax-eligible | 0.00312% | 32,018 |
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.Pro3769=
- Coding
- c.11307A>C
- MANE Select
- NM_001394062
- dbSNP
- rs148218605
- Type
- single nucleotide variant
- Location
- chr1:39353114 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
Similar variants
- MACF1 p.Pro3769Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro3769 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown