Is AFF4 p.Asp221fs (c.661del) pathogenic?

AFF4 p.Asp221fs (c.661del) is classified Uncertain significance in AFF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). Absent from gnomAD.

How common is AFF4 p.Asp221fs (c.661del) in the general population?

AFF4 p.Asp221fs (c.661del) is absent from gnomAD (gnomAD).

AFF4 p.Asp221fs

c.661del · rs2532575405 · VCV2442729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AFF4
Protein: p.Asp221fs
Coding: c.661del
MANE Select: NM_014423
dbSNP: rs2532575405
Type: Deletion
Location: chr5:132934404 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 221: the 'disordered' region

Full AFF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFF4 c.1227-99del Benign ★★ same type
AFF4 c.963+10_963+11del Likely benign ★★ same type
AFF4 c.1050+1_1050+5del Uncertain significance ★ same type
AFF4 c.1051_1053del Uncertain significance ★ same type
AFF4 p.Gln149_Gly160del Uncertain significance ★ same type
AFF4 p.His294fs Uncertain significance ★ same type
AFF4 p.Leu9fs Uncertain significance ★ same type
AFF4 p.Pro675del 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/aff4-p-asp221fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown