P4HTM p.Ala233=
c.699G>A · rs142286241 · VCV2498931
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.01 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.6 | GERP -4.7 |
| Overall | ||
| CADD | 1.638 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00903%
Overall
0.0057%
92/1,613,636 alleles · ultra-rare
exomes 73/1,461,342 · genomes 19/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| African / African-American | 0.0187% | 5,360 |
| Admixed American | 0.0167% | 6,002 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,499 |
| European (non-Finnish) | 0.00509% | 19,659 |
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.Ala233=
- Coding
- c.699G>A
- MANE Select
- NM_177939
- dbSNP
- rs142286241
- Type
- single nucleotide variant
- Location
- chr3:49002571 (GRCh38)
- Gene constraint
- LOEUF 0.815 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.94 · 1 PDB
- Residue 233
- an α-helix; the ef-hand 2 domain
Similar variants
- P4HTM p.Ala233Thr Uncertain significance ★★ ⚠ same residue
- P4HTM p.Pro413Leu Pathogenic/Likely pathogenic ★★ same type
- P4HTM p.Trp220Ter Pathogenic ★★ 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-ala233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown