MLPH p.Lys44=
c.132G>A · rs145091337 · VCV778284
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.84%, amr) — too common for a highly-penetrant pathogenic allele
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 4.7 | GERP -0.23, phastCons 1 |
| Overall | ||
| CADD | 9.239 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.84%
Admixed American · 3,502/60,016 alleles
Filtering AF
5.67%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.61%
Overall
0.251%
4,043/1,613,430 alleles · common
exomes 3,306/1,461,096 · genomes 737/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 5.84% | 17 |
| South Asian | 0.264% | 379 |
| Remaining individualsnot grpmax-eligible | 0.186% | 539 |
| African / African-American | 0.0919% | 1,088 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.00932% | 10,728 |
| East Asian | 0.00891% | 11,221 |
| Finnishnot grpmax-eligible | 0.00158% | 63,276 |
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.Lys44=
- Coding
- c.132G>A
- MANE Select
- NM_024101
- dbSNP
- rs145091337
- Type
- single nucleotide variant
- Location
- chr2:237510595 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
- Residue 44
- the rabbd domain
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-lys44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown