ZFPM2 p.Pro128=
c.384G>A · rs199814804 · VCV1660264
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0662%, mid)
Conditions
1
46,XY sex reversal 9
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -3.4 |
| Overall | ||
| CADD | 2.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0662%
Middle Eastern · 4/6,040 alleles
Filtering AF
0.0226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00285%
46/1,612,864 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0662% | 1,510 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,404 |
| African / African-American | 0.00934% | 10,704 |
| South Asian | 0.0088% | 11,364 |
| European (non-Finnish) | 0.00178% | 56,163 |
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
- ZFPM2
- Protein
- p.Pro128=
- Coding
- c.384G>A
- MANE Select
- NM_012082
- dbSNP
- rs199814804
- Type
- single nucleotide variant
- Location
- chr8:105561445 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.93
Similar variants
- ZFPM2 p.Pro128Leu Uncertain significance ★★ ⚠ same residue
- ZFPM2 p.Arg117Gln Uncertain significance ★★ ⚠ same condition
- ZFPM2 p.Asn136Ser Uncertain significance ★★ ⚠ same condition
- ZFPM2 p.Asp96Tyr Uncertain significance ★★ ⚠ same condition
- ZFPM2 p.Gln707Glu Uncertain significance ★★ ⚠ same condition
- ZFPM2 p.Gly164Arg Uncertain significance ★★ ⚠ same condition
- ZFPM2 p.Gly531Asp Uncertain significance ★★ ⚠ same condition
- ZFPM2 p.Gly547Arg Uncertain significance ★★ ⚠ same condition
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/zfpm2-p-pro128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown