AFF4 p.Leu270=
c.810G>A · rs114858484 · VCV707612
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.86%, afr)
Conditions
1
cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome
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 0.23 | GERP -1.2, phastCons 0.98 |
| Overall | ||
| CADD | 5.756 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.86%
African / African-American · 2,144/75,030 alleles
Filtering AF
2.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.72%
Overall
0.186%
2,998/1,614,154 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.86% | 35 |
| Admixed American | 0.312% | 321 |
| Remaining individualsnot grpmax-eligible | 0.206% | 485 |
| Middle Eastern | 0.181% | 551 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0676% | 1,480 |
| European (non-Finnish) | 0.0424% | 2,360 |
| South Asian | 0.00769% | 13,012 |
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
- AFF4
- Protein
- p.Leu270=
- Coding
- c.810G>A
- MANE Select
- NM_014423
- dbSNP
- rs114858484
- Type
- single nucleotide variant
- Location
- chr5:132934255 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.62 · 9 PDB
- Residue 270
- the 'disordered' region
Similar variants
- AFF4 p.Arg258Trp Pathogenic/Likely pathogenic ★★ same condition
- AFF4 p.Met260Val Likely pathogenic ★★ ⚠ same condition
- AFF4 p.Pro253Leu Pathogenic/Likely pathogenic ★★ same condition
- AFF4 p.Thr254Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AFF4 c.1133+3A>G Uncertain significance ★★ same condition
- AFF4 p.Ala114Thr Uncertain significance ★★ ⚠ same condition
- AFF4 p.Ala114Val Uncertain significance ★★ ⚠ same condition
- AFF4 p.Ala27Thr Uncertain significance ★★ ⚠ same condition
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/aff4-p-leu270 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown