ZFX p.Ser643=
c.1929G>A · VCV3904814
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00492%, nfe)
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 -3.2 | GERP -3.7 |
| Overall | ||
| CADD | 2.294 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00492%
European (non-Finnish) · 44/894,747 alleles
Filtering AF
0.00373%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00332%
Overall
0.00397%
48/1,208,117 alleles · very rare
exomes 46/1,098,225 · genomes 2/109,892 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00492% | 20,335 |
| Remaining individualsnot grpmax-eligible | 0.0042% | 23,789 |
| East Asian | 0.00296% | 33,732 |
| South Asian | 0.00177% | 56,608 |
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
- ZFX
- Protein
- p.Ser643=
- Coding
- c.1929G>A
- MANE Select
- NM_003410
- Type
- single nucleotide variant
- Location
- chrX:24210887 (GRCh38)
- Structure
- AlphaFold pLDDT 54.07
Similar variants
- ZFX p.Ser643Leu Uncertain significance ★ ⚠ same residue
- ZFX p.Tyr774Cys Pathogenic ★★ same type
- ZFX p.Ile414Val Uncertain significance ★★ ⚠ same type
- ZFX p.Ile64= Benign ★★ same type
- ZFX p.Pro788Arg Likely pathogenic ★ same type
- ZFX p.Thr771Met Pathogenic ★ ⚠ same type
- ZFX p.Val153Gly Likely pathogenic ★ ⚠ same type
- ZFX c.1234+4A>G 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/zfx-p-ser643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown