MACF1 p.Gln6433=
c.19299G>A · rs139563893 · VCV2057324
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.03%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.286 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.27 | donor loss, 25 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -0.2, phastCons 1 |
| Overall | ||
| CADD | 2.623 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.03%
African / African-American · 1,521/75,004 alleles
Filtering AF
1.94%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.91%
Overall
0.106%
1,717/1,613,064 alleles · low-frequency
exomes 843/1,460,736 · genomes 874/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.03% | 49 |
| Remaining individualsnot grpmax-eligible | 0.141% | 710 |
| Admixed American | 0.112% | 894 |
| Middle Eastern | 0.066% | 1,514 |
| Finnishnot grpmax-eligible | 0.00782% | 12,790 |
| European (non-Finnish) | 0.00271% | 36,860 |
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.Gln6433=
- Coding
- c.19299G>A
- MANE Select
- NM_001394062
- dbSNP
- rs139563893
- Type
- single nucleotide variant
- Location
- chr1:39442908 (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-gln6433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown