MLPH p.Thr472=
c.1416G>A · rs139181999 · VCV435878
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
rare (popmax 0.495%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.028 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.4 |
| Overall | ||
| CADD | 0.092 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.495%
Middle Eastern · 27/5,456 alleles
Filtering AF
0.349%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.3%
Overall
0.0304%
490/1,609,460 alleles · rare
exomes 355/1,457,160 · genomes 135/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.495% | 202 |
| African / African-American | 0.254% | 394 |
| Admixed American | 0.175% | 572 |
| Remaining individualsnot grpmax-eligible | 0.0722% | 1,384 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0136% | 7,373 |
| European (non-Finnish) | 0.00984% | 10,158 |
| South Asian | 0.00442% | 22,641 |
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.Thr472=
- Coding
- c.1416G>A
- MANE Select
- NM_024101
- dbSNP
- rs139181999
- Type
- single nucleotide variant
- Location
- chr2:237540927 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
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-thr472 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown