PHYH p.Lys218=
c.654G>A · rs1048643445 · VCV2802646
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 0.38 | GERP 0.56, phastCons 0.025 |
| Overall | ||
| CADD | 7.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,006 alleles
Overall
0.000124%
2/1,613,864 alleles · very rare
exomes 1/1,461,654 · genomes 1/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,006 |
| European (non-Finnish) | 8.47e-05% | 1,180,043 |
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.Lys218=
- Coding
- c.654G>A
- MANE Select
- NM_006214
- dbSNP
- rs1048643445
- Type
- single nucleotide variant
- Location
- chr10:13288384 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.33 · 1 PDB
- Residue 218
- an α-helix
Similar variants
- 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
- PHYH p.Arg275Gln 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-lys218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown