MLPH p.Pro262=
c.786G>A · VCV3630540
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0847%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.01 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.8 | GERP -4.2 |
| Overall | ||
| CADD | 0.931 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0847%
East Asian · 38/44,888 alleles
Filtering AF
0.0673%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0612%
Overall
0.00867%
140/1,614,138 alleles · ultra-rare
exomes 96/1,461,796 · genomes 44/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0847% | 1,181 |
| African / African-American | 0.0839% | 1,192 |
| Admixed American | 0.0183% | 5,457 |
| Middle Eastern | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,814 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| Finnishnot grpmax-eligible | 0.00313% | 31,978 |
| South Asian | 0.0022% | 45,540 |
| European (non-Finnish) | 0.00119% | 84,288 |
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.Pro262=
- Coding
- c.786G>A
- MANE Select
- NM_024101
- Type
- single nucleotide variant
- Location
- chr2:237525711 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
- Residue 262
- the 'disordered' region
Similar variants
- MLPH p.Pro262Gln 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-pro262 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown