PTH p.His40=
c.120T>C · rs977965204 · VCV758235
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
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 0.92 | GERP -3.6, phastCons 0.36 |
| Overall | ||
| CADD | 6.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,008 alleles
Overall
6.2e-05%
1/1,614,106 alleles · very rare
exomes 1/1,461,842 · genomes 0/152,264 · joint denominator
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
- PTH
- Protein
- p.His40=
- Coding
- c.120T>C
- MANE Select
- NM_000315
- dbSNP
- rs977965204
- Type
- single nucleotide variant
- Location
- chr11:13492633 (GRCh38)
- Gene constraint
- LOEUF 1.32 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 72.93 · 26 PDB
- Residue 40
- an α-helix
Similar variants
- PTH p.His40Tyr Uncertain significance ★ ⚠ same residue
- PTH p.Arg56Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- PTH c.-33C>T Uncertain significance ★★ same type
- PTH p.Ala77Asp Uncertain significance ★★ ⚠ same type
- PTH c.86+9T>G Benign ★★ same type
- PTH c.87-50G>A Benign ★★ same type
- PTH c.-5-10G>A Benign/Likely benign ★★ same type
- PTH c.-5-98G>A 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/pth-p-his40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown