AFF2 p.Leu451=
c.1353C>G · rs138980868 · VCV772438
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Overall | ||
| CADD | 2.538 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
African / African-American · 579/56,766 alleles
Filtering AF
0.951%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.924%
Overall
0.0519%
621/1,197,545 alleles · low-frequency
exomes 296/1,086,221 · genomes 325/111,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.02% | 98 |
| Remaining individualsnot grpmax-eligible | 0.0593% | 1,686 |
| Admixed American | 0.0241% | 4,147 |
| European (non-Finnish) | 0.000339% | 294,827 |
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
- AFF2
- Protein
- p.Leu451=
- Coding
- c.1353C>G
- MANE Select
- NM_002025
- dbSNP
- rs138980868
- Type
- single nucleotide variant
- Location
- chrX:148885979 (GRCh38)
- Structure
- AlphaFold pLDDT 49.27
Similar variants
- AFF2 c.3267+5G>C Uncertain significance ★★ same type
- AFF2 p.Ala1197Thr Uncertain significance ★★ ⚠ same type
- AFF2 p.Ala171Pro Uncertain significance ★★ ⚠ same type
- AFF2 p.Arg1238Cys Uncertain significance ★★ ⚠ same type
- AFF2 p.Arg1295Cys Uncertain significance ★★ ⚠ same type
- AFF2 p.Arg670His Uncertain significance ★★ ⚠ same type
- AFF2 p.Asn77Ile Uncertain significance ★★ ⚠ same type
- AFF2 p.Asp187Glu 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/aff2-p-leu451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown