MLPH p.Pro513=
c.1539G>T · rs151070956 · VCV1336244
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000346%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.064 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.48 | donor gain · deltas |
| Pangolin | Δ0.33 | gain · loss 0.11 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.074 | GERP -3.6, phastCons 0.23 |
| Overall | ||
| CADD | 19.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000346%
European (non-Finnish) · 4/1,156,540 alleles
Filtering AF
8.1e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.5e-05%
Overall
0.000255%
4/1,567,524 alleles · very rare
exomes 4/1,415,670 · genomes 0/151,854 · joint denominator
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.Pro513=
- Coding
- c.1539G>T
- MANE Select
- NM_024101
- dbSNP
- rs151070956
- Type
- single nucleotide variant
- Location
- chr2:237542659 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
- Residue 513
- the 'disordered' region
Similar variants
- MLPH p.Pro513Leu Uncertain significance ★★ ⚠ same residue
- 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
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-pro513 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown