AFF4 p.Pro669=
c.2007C>T · rs739863 · VCV1170072
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 19.3%, sas) — too common for a highly-penetrant pathogenic allele
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 0.001 | GERP -3.5, phastCons 0.033 |
| Overall | ||
| CADD | 8.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19.3%
South Asian · 17,613/91,076 alleles
Filtering AF
19.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 19%
Overall
15.4%
247,801/1,613,896 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 19.3% | 5 |
| Middle Eastern | 18.3% | 5 |
| European (non-Finnish) | 16.5% | 6 |
| Remaining individualsnot grpmax-eligible | 14.7% | 7 |
| Finnishnot grpmax-eligible | 13.3% | 8 |
| East Asian | 12.5% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 11.9% | 8 |
| Amishnot grpmax-eligible | 9.45% | 11 |
| Admixed American | 8.16% | 12 |
| African / African-American | 3.47% | 29 |
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.Pro669=
- Coding
- c.2007C>T
- MANE Select
- NM_014423
- dbSNP
- rs739863
- Type
- single nucleotide variant
- Location
- chr5:132896623 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.62 · 9 PDB
- Residue 669
- the 'disordered' region
Similar variants
- AFF4 p.Pro669Ser Uncertain significance ★★ ⚠ same residue
- 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
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-pro669 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown