MLPH p.Asp379=
c.1137T>C · rs3817363 · VCV1274242
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 32%, eas) — 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. | ||
| REVEL | 0.072 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -1.1 |
| Overall | ||
| CADD | 1.877 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
32%
East Asian · 14,329/44,840 alleles
Filtering AF
31.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 31.3%
Overall
11.3%
181,824/1,613,120 alleles · common
exomes 162,235/1,461,036 · genomes 19,589/152,084 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 32% | 3 |
| Admixed American | 21.5% | 5 |
| South Asian | 21% | 5 |
| Middle Eastern | 16.3% | 6 |
| African / African-American | 15.3% | 7 |
| Remaining individualsnot grpmax-eligible | 13% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 12.4% | 8 |
| European (non-Finnish) | 9.07% | 11 |
| Finnishnot grpmax-eligible | 6.5% | 15 |
| Amishnot grpmax-eligible | 4.82% | 21 |
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.Asp379=
- Coding
- c.1137T>C
- MANE Select
- NM_024101
- dbSNP
- rs3817363
- Type
- single nucleotide variant
- Location
- chr2:237540380 (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.Asp379fs 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-asp379 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown