P4HTM p.Ala232=
c.696C>T · rs143357651 · VCV2653810
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.016 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -4.7 |
| Overall | ||
| CADD | 4.407 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00366%
59/1,613,800 alleles · ultra-rare
exomes 51/1,461,506 · genomes 8/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| African / African-American | 0.00666% | 15,008 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| South Asian | 0.00549% | 18,217 |
| East Asian | 0.00446% | 22,438 |
| European (non-Finnish) | 0.00356% | 28,088 |
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.Ala232=
- Coding
- c.696C>T
- MANE Select
- NM_177939
- dbSNP
- rs143357651
- Type
- single nucleotide variant
- Location
- chr3:49002568 (GRCh38)
- Gene constraint
- LOEUF 0.815 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 1 PDB
- Residue 232
- 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-ala232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown