AGGF1 p.Lys28=
c.84G>A · VCV3257612
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.745%, nfe)
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 3.9 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 13.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.745%
European (non-Finnish) · 8,795/1,179,940 alleles
Filtering AF
0.732%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.727%
Overall
0.59%
9,518/1,612,818 alleles · rare
exomes 9,021/1,460,432 · genomes 497/152,386 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.745% | 134 |
| Remaining individualsnot grpmax-eligible | 0.485% | 206 |
| Finnishnot grpmax-eligible | 0.365% | 274 |
| Admixed American | 0.162% | 619 |
| African / African-American | 0.0892% | 1,120 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0878% | 1,138 |
| South Asian | 0.0011% | 91,082 |
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
- AGGF1
- Protein
- p.Lys28=
- Coding
- c.84G>A
- MANE Select
- NM_018046
- Type
- single nucleotide variant
- Location
- chr5:77030850 (GRCh38)
- Gene constraint
- LOEUF 0.808 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.24
Similar variants
- AGGF1 c.313+6T>C Benign ★★ same type
- AGGF1 p.Glu133Lys Benign/Likely benign ★★ same type
- AGGF1 p.Met706Leu Benign ★★ same type
- AGGF1 p.Tyr112Cys Likely benign ★★ same type
- AGGF1 p.Tyr382= Benign/Likely benign ★★ same type
- AGGF1 p.Ala314Thr Uncertain significance ★ ⚠ same type
- AGGF1 p.Ala385Val Uncertain significance ★ ⚠ same type
- AGGF1 p.Ala5Gly 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/aggf1-p-lys28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown