PHYH p.Asp291=
c.873C>T · rs151301072 · VCV726787
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.1%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -3 |
| Overall | ||
| CADD | 1.186 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.1%
African / African-American · 75/75,020 alleles
Filtering AF
0.0817%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.075%
Overall
0.00675%
109/1,613,900 alleles · ultra-rare
exomes 62/1,461,656 · genomes 47/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.1% | 1,000 |
| Middle Eastern | 0.0165% | 6,058 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| European (non-Finnish) | 0.00229% | 43,698 |
| South Asian | 0.0022% | 45,536 |
| Admixed American | 0.00167% | 60,012 |
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
- PHYH
- Protein
- p.Asp291=
- Coding
- c.873C>T
- MANE Select
- NM_006214
- dbSNP
- rs151301072
- Type
- single nucleotide variant
- Location
- chr10:13281066 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.33 · 1 PDB
Similar variants
- PHYH p.Asp291Ala Uncertain significance ★ ⚠ same residue
- PHYH c.134+1G>A Likely pathogenic ★★ same type
- PHYH c.135-1G>C Pathogenic/Likely pathogenic ★★ same type
- PHYH c.135-2A>G Pathogenic ★★ same type
- PHYH c.497-1G>A Likely pathogenic ★★ same type
- PHYH c.497-2A>G Pathogenic/Likely pathogenic ★★ same type
- PHYH c.678+2T>C Likely pathogenic ★★ same type
- PHYH p.Ala277Glu Pathogenic/Likely pathogenic ★★ 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/phyh-p-asp291 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown