PAH p.His264=
c.792C>T · rs912042558 · VCV1635041
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Conditions
2
Inborn genetic diseases
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 3.6 | GERP -0.79, phastCons 1 |
| Overall | ||
| CADD | 8.225 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,010 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000137%
2/1,461,844 alleles · very rare
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
- PAH
- Protein
- p.His264=
- Coding
- c.792C>T
- MANE Select
- NM_000277
- dbSNP
- rs912042558
- Type
- single nucleotide variant
- Location
- chr12:102852865 (GRCh38)
- Gene constraint
- LOEUF 1.265 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.04 · 21 PDB
- Residue 264
- a UniProt-annotated variant site (in pah deficiency; severe; uncertain significance); a β-strand
Similar variants
- PAH p.His264Leu Uncertain significance ★★★ ⚠ same residue
- PAH p.His264Arg Uncertain significance ★ ⚠ same residue
- PAH p.His264fs Likely pathogenic same residue
- PAH p.His264Tyr Uncertain significance ★ ⚠ same residue
- PAH c.1065+1G>A Likely pathogenic ★★★ same condition
- PAH c.1065+1G>T Likely pathogenic ★★★ same condition
- PAH c.1065+3A>G Likely pathogenic ★★★ same condition
- PAH c.1066-11G>A Pathogenic ★★★ same condition
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/pah-p-his264 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown