MACF1 p.Glu381=
c.1143A>G · rs566899522 · VCV2180221
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.145%, eas)
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 3.5 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 8.743 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.145%
East Asian · 65/44,880 alleles
Filtering AF
0.117%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.106%
Overall
0.00589%
95/1,614,154 alleles · rare
exomes 84/1,461,882 · genomes 11/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.145% | 690 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| South Asian | 0.00329% | 30,359 |
| European (non-Finnish) | 0.00186% | 53,637 |
| Admixed American | 0.00167% | 60,012 |
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.Glu381=
- Coding
- c.1143A>G
- MANE Select
- NM_001394062
- dbSNP
- rs566899522
- Type
- single nucleotide variant
- Location
- chr1:39285094 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
- Residue 381
- an α-helix
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-glu381 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown