MAK p.Phe549=
c.1647T>C · rs1014087976 · VCV1139701
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00274%, afr)
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 0.42 | GERP -2.1, phastCons 0.81 |
| Overall | ||
| CADD | 5.454 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00274%
African / African-American · 2/72,952 alleles
Filtering AF
0.000516%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000377%
Overall
0.000914%
14/1,532,178 alleles · very rare
exomes 12/1,379,976 · genomes 2/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00274% | 36,476 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,838 |
| European (non-Finnish) | 0.000962% | 103,989 |
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
- MAK
- Protein
- p.Phe549=
- Coding
- c.1647T>C
- MANE Select
- NM_001242957
- dbSNP
- rs1014087976
- Type
- single nucleotide variant
- Location
- chr6:10773059 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.74
Similar variants
- MAK c.101+1G>A Likely pathogenic ★★ same type
- MAK c.156+2T>C Likely pathogenic ★★ same type
- MAK c.831+1G>C Likely pathogenic ★★ same type
- MAK c.832-1G>C Likely pathogenic ★★ same type
- MAK p.Arg166His Pathogenic ★★ same type
- MAK p.Arg272Ter Pathogenic/Likely pathogenic ★★ same type
- MAK p.Arg3Ter Pathogenic/Likely pathogenic ★★ same type
- MAK p.Asn130His Likely pathogenic ★★ 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/mak-p-phe549 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown