ZFPM2 p.Pro537=
c.1611C>T · VCV4901408
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -12 | GERP -4 |
| Overall | ||
| CADD | 0.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000682%
11/1,613,600 alleles · ultra-rare
exomes 9/1,461,520 · genomes 2/152,080 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| South Asian | 0.00329% | 30,358 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
| European (non-Finnish) | 0.000509% | 196,647 |
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.Pro537=
- Coding
- c.1611C>T
- MANE Select
- NM_012082
- Type
- single nucleotide variant
- Location
- chr8:105801693 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.93
Similar variants
- ZFPM2 p.Arg112Ter Pathogenic/Likely pathogenic ★★ same type
- ZFPM2 p.Arg117Gln Uncertain significance ★★ ⚠ same type
- ZFPM2 p.Arg222His Uncertain significance ★★ ⚠ same type
- ZFPM2 p.Asn136Ser Uncertain significance ★★ ⚠ same type
- ZFPM2 p.Asp96Tyr Uncertain significance ★★ ⚠ same type
- ZFPM2 p.Gln707Glu Uncertain significance ★★ ⚠ same type
- ZFPM2 p.Gly164Arg Uncertain significance ★★ ⚠ same type
- ZFPM2 p.Gly531Asp 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/zfpm2-p-pro537 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown