MLPH p.Tyr357=
c.1071C>T · rs77397270 · VCV713889
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.16%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.03 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.45 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -0.29 | GERP 0.78 |
| Overall | ||
| CADD | 0.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.16%
East Asian · 969/44,874 alleles
Filtering AF
2.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2%
Overall
0.063%
1,017/1,613,976 alleles · low-frequency
exomes 929/1,461,668 · genomes 88/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 2.16% | 46 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,083 |
| South Asian | 0.0132% | 7,589 |
| Admixed American | 0.005% | 20,008 |
| African / African-American | 0.00133% | 75,034 |
| European (non-Finnish) | 0.00017% | 589,960 |
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.Tyr357=
- Coding
- c.1071C>T
- MANE Select
- NM_024101
- dbSNP
- rs77397270
- Type
- single nucleotide variant
- Location
- chr2:237534614 (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-tyr357 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown