MLPH p.Phe591=
c.1773C>T · rs139682271 · VCV770135
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.55%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.3 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.9 | GERP -3.3 |
| Overall | ||
| CADD | 0.581 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.55%
Admixed American · 930/59,998 alleles
Filtering AF
1.47%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.43%
Overall
0.0641%
1,034/1,613,654 alleles · low-frequency
exomes 869/1,461,460 · genomes 165/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 1.55% | 65 |
| Remaining individualsnot grpmax-eligible | 0.0608% | 1,645 |
| African / African-American | 0.0213% | 4,687 |
| European (non-Finnish) | 0.00424% | 23,593 |
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
- MLPH
- Protein
- p.Phe591=
- Coding
- c.1773C>T
- MANE Select
- NM_024101
- dbSNP
- rs139682271
- Type
- single nucleotide variant
- Location
- chr2:237552434 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
- Residue 591
- the 'disordered' region
Similar variants
- MLPH p.Arg35Gln Pathogenic/Likely pathogenic ★★ same type
- MLPH p.Arg35Trp Pathogenic/Likely pathogenic ★★ same type
- MLPH p.Ala236Thr Uncertain significance ★★ ⚠ same type
- MLPH p.Ala520Ser Uncertain significance ★★ ⚠ same type
- MLPH p.Arg375Cys Uncertain significance ★★ ⚠ same type
- MLPH p.Arg507Trp Uncertain significance ★★ ⚠ same type
- MLPH p.Arg518Gly Uncertain significance ★★ ⚠ same type
- MLPH p.Asp194Asn 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/mlph-p-phe591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown