MLPH p.Ser223=
c.669C>T · VCV3770859
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.119%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.052 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.2, phastCons 0.81 |
| Overall | ||
| CADD | 6.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.119%
African / African-American · 89/75,032 alleles
Filtering AF
0.0987%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0913%
Overall
0.00787%
127/1,613,916 alleles · rare
exomes 74/1,461,662 · genomes 53/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.119% | 843 |
| Admixed American | 0.0217% | 4,618 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| European (non-Finnish) | 0.00161% | 62,104 |
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.Ser223=
- Coding
- c.669C>T
- MANE Select
- NM_024101
- Type
- single nucleotide variant
- Location
- chr2:237520023 (GRCh38)
- Gene constraint
- LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.58
- Residue 223
- the 'disordered' region
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-ser223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown