PHRF1 p.Asp1255=
c.3765C>T · rs555491602 · VCV2641079
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0285%, sas)
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 -0.34 | |
| Overall | ||
| CADD | 0.713 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0285%
South Asian · 26/91,088 alleles
Filtering AF
0.0199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0171%
Overall
0.00553%
89/1,610,026 alleles · ultra-rare
exomes 76/1,457,710 · genomes 13/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0285% | 3,503 |
| African / African-American | 0.016% | 6,254 |
| East Asian | 0.0156% | 6,410 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,806 |
| Finnishnot grpmax-eligible | 0.00832% | 12,020 |
| Admixed American | 0.00666% | 15,007 |
| European (non-Finnish) | 0.00229% | 43,698 |
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
- PHRF1
- Protein
- p.Asp1255=
- Coding
- c.3765C>T
- MANE Select
- NM_001286581
- dbSNP
- rs555491602
- Type
- single nucleotide variant
- Location
- chr11:609221 (GRCh38)
- Gene constraint
- LOEUF 0.573 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 46.11
Similar variants
- PHRF1 p.Asp1255Glu Likely benign ★ same residue
- PHRF1 p.Ala1355= Benign ★★ same type
- PHRF1 p.Gly1209Arg Benign ★★ same type
- PHRF1 p.Ser1168Leu Benign ★★ same type
- PHRF1 p.Ser1457Gly Likely benign ★★ same type
- PHRF1 p.Thr959= Likely benign ★★ same type
- PHRF1 p.Ala114Ser Uncertain significance ★ ⚠ same type
- PHRF1 p.Ala114Val Uncertain significance ★ ⚠ 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/phrf1-p-asp1255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown