PIGT p.Pro435=
c.1305G>A · rs144302866 · VCV750207
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
1
multiple congenital anomalies-hypotonia-seizures syndrome 3
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 -4.3 |
| Overall | ||
| CADD | 5.636 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.00112%
18/1,613,978 alleles · ultra-rare
exomes 15/1,461,880 · genomes 3/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.00401% | 24,964 |
| Admixed American | 0.00333% | 29,997 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| South Asian | 0.0022% | 45,543 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
| European (non-Finnish) | 0.000593% | 168,571 |
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
- PIGT
- Protein
- p.Pro435=
- Coding
- c.1305G>A
- MANE Select
- NM_015937
- dbSNP
- rs144302866
- Type
- single nucleotide variant
- Location
- chr20:45424286 (GRCh38)
- Gene constraint
- LOEUF 1.084 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.71 · 4 PDB
- Residue 435
- a UniProt-annotated variant site (in mcahs3; loss of function in gpi-anchor attachment to protein); a UniProt-annotated variant site (in mcahs3)
Similar variants
- PIGT p.Pro435Leu Uncertain significance ★★ ⚠ same residue
- PIGT c.188-2A>G Pathogenic/Likely pathogenic ★★ same condition
- PIGT c.494-2A>G Pathogenic ★★ same condition
- PIGT p.Arg172Cys Pathogenic/Likely pathogenic ★★ same condition
- PIGT p.Arg266Ter Pathogenic/Likely pathogenic ★★ same condition
- PIGT p.Arg330Ter Pathogenic ★★ same condition
- PIGT p.Arg448Trp Pathogenic/Likely pathogenic ★★ same condition
- PIGT p.Glu237Gln Likely pathogenic ★★ 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/pigt-p-pro435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown