MACF1 p.Ala2398=
c.7194C>A · rs141334491 · VCV1319797
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.509%, nfe)
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 -0.19 | GERP -1.7, phastCons 0.053 |
| Overall | ||
| CADD | 6.505 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.509%
European (non-Finnish) · 6,004/1,180,032 alleles
Filtering AF
0.498%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.494%
Overall
0.414%
6,680/1,614,170 alleles · rare
exomes 6,185/1,461,872 · genomes 495/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.509% | 197 |
| Finnishnot grpmax-eligible | 0.381% | 262 |
| Remaining individualsnot grpmax-eligible | 0.37% | 271 |
| Middle Eastern | 0.165% | 606 |
| Ashkenazi Jewishnot grpmax-eligible | 0.162% | 617 |
| Admixed American | 0.12% | 834 |
| African / African-American | 0.0506% | 1,975 |
| South Asian | 0.0362% | 2,760 |
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.Ala2398=
- Coding
- c.7194C>A
- MANE Select
- NM_001394062
- dbSNP
- rs141334491
- Type
- single nucleotide variant
- Location
- chr1:39333782 (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-ala2398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown