MPZL2 p.Ser141=
c.423C>T · rs370925743 · VCV3048028
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0483%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.38 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.025 | GERP -4, phastCons 0.22 |
| Overall | ||
| CADD | 10.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0483%
Admixed American · 29/60,012 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0299%
Overall
0.00942%
152/1,613,780 alleles · ultra-rare
exomes 123/1,461,600 · genomes 29/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0483% | 2,069 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,411 |
| European (non-Finnish) | 0.00949% | 10,536 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| African / African-American | 0.00267% | 37,491 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
| South Asian | 0.0011% | 91,064 |
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
- MPZL2
- Protein
- p.Ser141=
- Coding
- c.423C>T
- MANE Select
- NM_005797
- dbSNP
- rs370925743
- Type
- single nucleotide variant
- Location
- chr11:118262451 (GRCh38)
- Gene constraint
- LOEUF 1.703 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.54
- Residue 141
- a UniProt-annotated variant site (in dfnb111; pathogenic); the ig-like v-type domain
Similar variants
- MPZL2 c.226-2A>T Pathogenic/Likely pathogenic ★★ same type
- MPZL2 p.Gln74Ter Pathogenic/Likely pathogenic ★★ same type
- MPZL2 p.Pro129Arg Likely pathogenic ★★ same type
- MPZL2 p.Arg103Gln Uncertain significance ★★ ⚠ same type
- MPZL2 p.Arg33Gln Uncertain significance ★★ ⚠ same type
- MPZL2 p.Ile151Thr Uncertain significance ★★ same type
- MPZL2 p.Gln85= Benign ★★ same type
- MPZL2 p.Leu13= Benign/Likely benign ★★ 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/mpzl2-p-ser141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown