P4HTM p.Ala163=
c.489G>A · VCV4962531
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.163%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.632 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.7 | GERP -5.5 |
| Overall | ||
| CADD | 3.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.163%
East Asian · 73/44,890 alleles
Filtering AF
0.133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.122%
Overall
0.00843%
136/1,613,888 alleles · rare
exomes 107/1,461,590 · genomes 29/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.163% | 615 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,717 |
| South Asian | 0.0187% | 5,358 |
| African / African-American | 0.00666% | 15,007 |
| European (non-Finnish) | 0.00153% | 65,556 |
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.Ala163=
- Coding
- c.489G>A
- MANE Select
- NM_177939
- Type
- single nucleotide variant
- Location
- chr3:49001490 (GRCh38)
- Gene constraint
- LOEUF 0.815 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 1 PDB
- Residue 163
- an α-helix
Similar variants
- P4HTM p.Ala163Val 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-ala163 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown