P4HTM p.Ser304=
c.912G>A · rs149713068 · VCV3239147
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.132%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -4.8 |
| Overall | ||
| CADD | 4.412 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.132%
Middle Eastern · 8/6,058 alleles
Filtering AF
0.0657%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.048%
Overall
0.0101%
162/1,610,732 alleles · rare
exomes 150/1,458,472 · genomes 12/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.132% | 757 |
| South Asian | 0.0176% | 5,691 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,245 |
| European (non-Finnish) | 0.0102% | 9,830 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0102% | 9,851 |
| Admixed American | 0.005% | 20,005 |
| East Asian | 0.00223% | 44,870 |
| African / African-American | 0.00133% | 75,006 |
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.Ser304=
- Coding
- c.912G>A
- MANE Select
- NM_177939
- dbSNP
- rs149713068
- Type
- single nucleotide variant
- Location
- chr3:49004885 (GRCh38)
- Gene constraint
- LOEUF 0.815 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 1 PDB
Similar variants
- P4HTM p.Ser304Leu Uncertain significance ★ ⚠ same residue
- 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
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-ser304 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown