AFF3 p.Lys543=
c.1629A>G · rs754626263 · VCV2651191
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0137%, 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 -1.8 | GERP -4.9 |
| Overall | ||
| CADD | 2.108 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0137%
European (non-Finnish) · 161/1,175,004 alleles
Filtering AF
0.0119%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0113%
Overall
0.0105%
168/1,605,344 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0137% | 7,298 |
| Remaining individualsnot grpmax-eligible | 0.00806% | 12,402 |
| Finnishnot grpmax-eligible | 0.00158% | 63,468 |
| African / African-American | 0.00134% | 74,614 |
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
- AFF3
- Protein
- p.Lys543=
- Coding
- c.1629A>G
- MANE Select
- NM_001386135
- dbSNP
- rs754626263
- Type
- single nucleotide variant
- Location
- chr2:99594032 (GRCh38)
- Gene constraint
- LOEUF 0.318 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.20
- Residue 543
- the 'disordered' region
Similar variants
- AFF3 p.Lys543Ile Uncertain significance ★ ⚠ same residue
- AFF3 p.Ala233Thr Pathogenic ★★ ⚠ same type
- AFF3 p.Ala233Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- AFF3 p.Ile1147Asn Uncertain significance ★★ ⚠ same type
- AFF3 p.Leu370Phe Uncertain significance ★★ ⚠ same type
- AFF3 p.Pro321Leu Uncertain significance ★★ ⚠ same type
- AFF3 p.Ser222Thr Uncertain significance ★★ ⚠ same type
- AFF3 p.Thr950Met 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/aff3-p-lys543 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown