MLPH p.Ser503=
c.1509G>A · rs201166379 · VCV2058867
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.101%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.011 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.7 |
| Overall | ||
| CADD | 0.133 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.101%
Middle Eastern · 6/5,922 alleles
Filtering AF
0.044%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0352%
Overall
0.0067%
107/1,597,770 alleles · rare
exomes 97/1,445,644 · genomes 10/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.101% | 987 |
| Admixed American | 0.0554% | 1,805 |
| Remaining individualsnot grpmax-eligible | 0.0113% | 8,842 |
| South Asian | 0.0102% | 9,814 |
| African / African-American | 0.00802% | 12,466 |
| East Asian | 0.00452% | 22,145 |
| European (non-Finnish) | 0.00384% | 26,070 |
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.Ser503=
- Coding
- c.1509G>A
- MANE Select
- NM_024101
- dbSNP
- rs201166379
- Type
- single nucleotide variant
- Location
- chr2:237542629 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
- Residue 503
- the 'disordered' region
Similar variants
- MLPH p.Ser503Leu Benign/Likely benign ★★ same residue
- MLPH p.Ser503Ter Pathogenic ★ 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
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-ser503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown