Is AFF4 p.Phe967fs (c.2898dup) pathogenic?

AFF4 p.Phe967fs (c.2898dup) is classified Uncertain significance in AFF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01).

AFF4 p.Phe967fs

c.2898dup · VCV3389598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 16 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 5.6, phastCons 1

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

Variant & gene context

Gene: AFF4
Protein: p.Phe967fs
Coding: c.2898dup
MANE Select: NM_014423
Type: Duplication
Location: chr5:132887880 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 967: an α-helix

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

Similar variants

AFF4 p.Asn423_Ser424insTyr Uncertain significance ★★ same type
AFF4 c.1227-69dup Benign ★★ same type
AFF4 c.963+12dup Benign ★★ same type
AFF4 p.Glu172_His173insGln Conflicting classifications of pathogenicity ★ same type
AFF4 p.Ser133_Gln134insSer Uncertain significance ★ same type
AFF4 p.Ser246fs Uncertain significance ★ same type
AFF4 c.124-5dup Benign ★ same type
AFF4 c.2934-20_2934-19dup Likely benign ★ 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-phe967fs (accessed [today's date]).

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