P4HTM p.Glu225=
c.675G>A · VCV4962535
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000508%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.243 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 9.049 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000508%
European (non-Finnish) · 6/1,179,990 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,614,140 alleles · very rare
exomes 6/1,461,792 · genomes 0/152,348 · joint denominator
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
- P4HTM
- Protein
- p.Glu225=
- Coding
- c.675G>A
- MANE Select
- NM_177939
- Type
- single nucleotide variant
- Location
- chr3:49002547 (GRCh38)
- Gene constraint
- LOEUF 0.815 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 1 PDB
- Residue 225
- an α-helix; the ef-hand 2 domain
Similar variants
- P4HTM p.Pro413Leu Pathogenic/Likely pathogenic ★★ same type
- P4HTM p.Trp220Ter Pathogenic ★★ same type
- P4HTM p.Ala233Thr Uncertain significance ★★ ⚠ same type
- P4HTM p.Arg493Gln Uncertain significance ★★ ⚠ same type
- P4HTM p.Ser171Gly Uncertain significance ★★ ⚠ same type
- P4HTM p.Ser184Thr Uncertain significance ★★ ⚠ same type
- P4HTM p.Ser269Thr Uncertain significance ★★ ⚠ same type
- P4HTM c.436+8C>T Benign/Likely benign ★★ 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/p4htm-p-glu225 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown