GMDS p.Pro268=
c.804G>A · rs143104834 · VCV2656175
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, afr)
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 -8.7 | GERP -3.8 |
| Overall | ||
| CADD | 0.125 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,872 alleles
Filtering AF
0.00816%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00634%
Overall
0.00602%
97/1,610,116 alleles · ultra-rare
exomes 86/1,457,924 · genomes 11/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,807 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,471 |
| South Asian | 0.00659% | 15,163 |
| European (non-Finnish) | 0.0062% | 16,117 |
| East Asian | 0.00223% | 44,862 |
| Finnishnot grpmax-eligible | 0.00156% | 63,986 |
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
- GMDS
- Protein
- p.Pro268=
- Coding
- c.804G>A
- MANE Select
- NM_001500
- dbSNP
- rs143104834
- Type
- single nucleotide variant
- Location
- chr6:1742554 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI 0.54 (gnomAD)
- Structure
- AlphaFold pLDDT 94.59 · 7 PDB
Similar variants
- GMDS p.Pro268Leu Uncertain significance ★ ⚠ same residue
- GMDS p.Ala121Val Uncertain significance ★ ⚠ same type
- GMDS p.Ala125Val Uncertain significance ★ ⚠ same type
- GMDS p.Ala153Thr Uncertain significance ★ ⚠ same type
- GMDS p.Ala2Thr Uncertain significance ★ ⚠ same type
- GMDS p.Ala361Thr Uncertain significance ★ ⚠ same type
- GMDS p.Arg176Gln Uncertain significance ★ ⚠ same type
- GMDS p.Arg282Gln 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/gmds-p-pro268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown