PHYH p.Ala76=
c.228C>T · rs779247277 · VCV2790032
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00224%, sas)
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 -0.43 | GERP -3.5, phastCons 0.001 |
| Overall | ||
| CADD | 2.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00224%
South Asian · 2/89,458 alleles
Filtering AF
0.000371%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000139%
Overall
0.000195%
3/1,537,258 alleles · very rare
exomes 3/1,385,208 · genomes 0/152,050 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00224% | 44,729 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,976 |
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.Ala76=
- Coding
- c.228C>T
- MANE Select
- NM_006214
- dbSNP
- rs779247277
- Type
- single nucleotide variant
- Location
- chr10:13295513 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.33 · 1 PDB
- Residue 76
- an α-helix
Similar variants
- PHYH p.Ala76Val 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-ala76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown