PASK p.His447=
c.1341C>T · rs149765742 · VCV724081
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.14%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.97 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.064 | GERP -1.4 |
| Overall | ||
| CADD | 1.911 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.14%
African / African-American · 105/75,002 alleles
Filtering AF
0.118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.11%
Overall
0.0156%
252/1,614,072 alleles · rare
exomes 187/1,461,816 · genomes 65/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.14% | 714 |
| Middle Eastern | 0.033% | 3,031 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0304% | 3,290 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| East Asian | 0.0223% | 4,488 |
| Admixed American | 0.02% | 5,002 |
| European (non-Finnish) | 0.00797% | 12,553 |
| South Asian | 0.00439% | 22,769 |
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
- PASK
- Protein
- p.His447=
- Coding
- c.1341C>T
- MANE Select
- NM_015148
- dbSNP
- rs149765742
- Type
- single nucleotide variant
- Location
- chr2:241132996 (GRCh38)
- Gene constraint
- LOEUF 1.03 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.14 · 2 PDB
Similar variants
- PASK p.His447Tyr Uncertain significance ★ ⚠ same residue
- PASK c.3533+1G>A Uncertain significance ★★ same type
- PASK p.Arg1319His Benign ★★ same type
- PASK p.Arg937His Benign ★★ same type
- PASK p.Gly782Arg Benign ★★ same type
- PASK p.Pro101= Benign ★★ same type
- PASK p.Pro844= Benign ★★ same type
- PASK p.Ser582= 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/pask-p-his447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown