MACF1 p.Ala112=
c.336G>A · rs148817607 · VCV3250565
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.491%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.28 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.1 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 13.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.491%
African / African-American · 354/72,168 alleles
Filtering AF
0.448%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.432%
Overall
0.0274%
415/1,515,350 alleles · rare
exomes 215/1,363,048 · genomes 200/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.491% | 204 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,735 |
| Admixed American | 0.0348% | 2,874 |
| Middle Eastern | 0.0178% | 5,618 |
| South Asian | 0.00247% | 40,446 |
| European (non-Finnish) | 0.000616% | 162,422 |
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.Ala112=
- Coding
- c.336G>A
- MANE Select
- NM_001394062
- dbSNP
- rs148817607
- Type
- single nucleotide variant
- Location
- chr1:39251920 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
- Residue 112
- the 'disordered' region; the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region
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-ala112 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown