PIDD1 p.His72=
c.216C>T · VCV3777875
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0408%, 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 3.8 | GERP -0.81, phastCons 1 |
| Overall | ||
| CADD | 15.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0408%
European (non-Finnish) · 481/1,179,928 alleles
Filtering AF
0.0377%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0366%
Overall
0.0313%
505/1,613,298 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0408% | 2,453 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,805 |
| African / African-American | 0.00801% | 12,489 |
| Admixed American | 0.005% | 19,999 |
| East Asian | 0.00223% | 44,902 |
| Finnishnot grpmax-eligible | 0.00158% | 63,384 |
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
- PIDD1
- Protein
- p.His72=
- Coding
- c.216C>T
- MANE Select
- NM_145886
- Type
- single nucleotide variant
- Location
- chr11:804173 (GRCh38)
- Gene constraint
- LOEUF 1.237 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.02 · 2 PDB
Similar variants
- PIDD1 p.Arg637Ter Pathogenic/Likely pathogenic ★★ same type
- PIDD1 p.Arg862Trp Pathogenic ★★ same type
- PIDD1 p.Arg551Cys Uncertain significance ★★ ⚠ same type
- PIDD1 p.Arg605Gln Uncertain significance ★★ ⚠ same type
- PIDD1 p.Arg725Cys Uncertain significance ★★ same type
- PIDD1 p.Arg742Ser Uncertain significance ★★ ⚠ same type
- PIDD1 p.Arg821Trp Uncertain significance ★★ ⚠ same type
- PIDD1 p.Arg842His 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/pidd1-p-his72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown