P4HTM p.Leu469=
c.1407G>T · VCV3388469
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.497%, sas)
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 0.26 | GERP -4.8, phastCons 0.95 |
| Overall | ||
| CADD | 4.963 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.497%
South Asian · 453/91,092 alleles
Filtering AF
0.459%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.444%
Overall
0.0294%
474/1,613,526 alleles · rare
exomes 450/1,461,134 · genomes 24/152,392 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.497% | 201 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| East Asian | 0.00223% | 44,888 |
| African / African-American | 0.00133% | 75,082 |
| European (non-Finnish) | 8.47e-05% | 1,180,044 |
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.Leu469=
- Coding
- c.1407G>T
- MANE Select
- NM_177939
- Type
- single nucleotide variant
- Location
- chr3:49006805 (GRCh38)
- Gene constraint
- LOEUF 0.815 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 1 PDB
- Residue 469
- an α-helix
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-leu469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown