PHYH p.Pro173=
c.519C>T · rs764537504 · VCV2914900
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
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 -1.2 | GERP -3.1 |
| Overall | ||
| CADD | 6.438 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,050 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000867%
14/1,614,036 alleles · ultra-rare
exomes 11/1,461,848 · genomes 3/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,025 |
| East Asian | 0.00446% | 22,441 |
| South Asian | 0.0022% | 45,544 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00133% | 74,920 |
| European (non-Finnish) | 0.000508% | 196,675 |
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.Pro173=
- Coding
- c.519C>T
- MANE Select
- NM_006214
- dbSNP
- rs764537504
- Type
- single nucleotide variant
- Location
- chr10:13288519 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.33 · 1 PDB
- Residue 173
- a UniProt-annotated variant site (in rd)
Similar variants
- PHYH p.Pro173Ser Uncertain significance ★ ⚠ same residue
- PHYH p.Pro173Thr Conflicting classifications of pathogenicity ★ ⚠ 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
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-pro173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown