MLPH p.Arg507=
c.1521G>C · rs566121949 · VCV2896082
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00356%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.339 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP -0.32, phastCons 1 |
| Overall | ||
| CADD | 4.594 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00356%
Admixed American · 2/56,180 alleles
Filtering AF
0.00059%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000221%
Overall
0.000189%
3/1,587,806 alleles · very rare
exomes 2/1,435,772 · genomes 1/152,034 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00356% | 28,090 |
| European (non-Finnish) | 8.56e-05% | 1,167,829 |
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.Arg507=
- Coding
- c.1521G>C
- MANE Select
- NM_024101
- dbSNP
- rs566121949
- Type
- single nucleotide variant
- Location
- chr2:237542641 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
- Residue 507
- the 'disordered' region
Similar variants
- MLPH p.Arg507Trp Uncertain significance ★★ ⚠ same residue
- MLPH p.Arg507Gln 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.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-arg507 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown