MLPH c.1104+252T>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 33%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -1.3 |
| Non-coding constraint | Z 2.65 | 1 kb window · o/e 0.80 · regional · uncalibrated |
| Overall | ||
| CADD | 3.405 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
33%
African / African-American · 13,693/41,462 alleles
Filtering AF
32.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 32.4%
Overall
19.8%
30,093/152,068 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 33% | 3 |
| Remaining individualsnot grpmax-eligible | 17.8% | 6 |
| European (non-Finnish) | 16.5% | 6 |
| Amishnot grpmax-eligible | 15.7% | 6 |
| Middle Eastern | 14.3% | 7 |
| Finnishnot grpmax-eligible | 13.6% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 13.4% | 7 |
| South Asian | 13.3% | 8 |
| Admixed American | 11.5% | 9 |
| East Asian | 6.12% | 16 |
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
- Coding
- c.1104+252T>C
- MANE Select
- NM_024101
- dbSNP
- rs9646713
- Type
- single nucleotide variant
- Location
- chr2:237534899 (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-c-1104-plus-252t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown