PHRF1 p.Asp1350=
c.4050C>T · VCV3418006
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, 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 -14 | |
| Overall | ||
| CADD | 0.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,056 alleles
Filtering AF
0.00766%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00597%
Overall
0.00667%
107/1,603,210 alleles · ultra-rare
exomes 99/1,450,886 · genomes 8/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,028 |
| South Asian | 0.0133% | 7,531 |
| European (non-Finnish) | 0.00738% | 13,542 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,124 |
| African / African-American | 0.00267% | 37,484 |
| East Asian | 0.00224% | 44,722 |
| Admixed American | 0.00169% | 59,332 |
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.Asp1350=
- Coding
- c.4050C>T
- MANE Select
- NM_001286581
- Type
- single nucleotide variant
- Location
- chr11:609506 (GRCh38)
- Gene constraint
- LOEUF 0.573 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 46.11
- Residue 1350
- the 'disordered' region
Similar variants
- 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
- PHRF1 p.Ala1197Ser 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-asp1350 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown