AFF4 p.Ser1007=
c.3021T>C · rs370085438 · VCV2193386
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, amr)
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 2.3 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 10.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
Admixed American · 14/59,988 alleles
Filtering AF
0.0141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0112%
Overall
0.00149%
24/1,613,960 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0233% | 4,285 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| East Asian | 0.00223% | 44,894 |
| African / African-American | 0.00133% | 74,938 |
| European (non-Finnish) | 0.000508% | 196,670 |
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.Ser1007=
- Coding
- c.3021T>C
- MANE Select
- NM_014423
- dbSNP
- rs370085438
- Type
- single nucleotide variant
- Location
- chr5:132886388 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.62 · 9 PDB
- Residue 1007
- an α-helix
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-ser1007 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown