Is AFF3 p.Glu606fs (c.1815del) pathogenic?

AFF3 p.Glu606fs (c.1815del) is classified Uncertain significance in AFF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). Very rare (popmax 0.00111%, sas); Associated with AFF3-related disorder.

What condition is associated with AFF3 p.Glu606fs (c.1815del)?

AFF3 p.Glu606fs (c.1815del) is associated with AFF3-related disorder (ClinVar).

How common is AFF3 p.Glu606fs (c.1815del) in the general population?

AFF3 p.Glu606fs (c.1815del) is very rare (popmax 0.00111%, sas) (gnomAD).

AFF3 p.Glu606fs

c.1815del · rs2546102839 · VCV2630383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

AFF3-related disorder

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 15 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,202 alleles

Overall 6.92e-05% 1/1,445,582 alleles · very rare

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: AFF3
Protein: p.Glu606fs
Coding: c.1815del
MANE Select: NM_001386135
dbSNP: rs2546102839
Type: Deletion
Location: chr2:99593846 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 606: the 'disordered' region

Full AFF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AFF3-related disorder

Similar variants

AFF3 p.Glu606Lys Uncertain significance ★ ⚠ same residue
AFF3 p.Thr594fs Benign same condition
AFF3 p.Met238Arg Likely pathogenic ★ ⚠ same condition
AFF3 p.Pro231Arg Pathogenic ★ same condition
AFF3 p.Asn937del Uncertain significance ★ same condition
AFF3 p.His211Asn Uncertain significance ★ ⚠ same condition
AFF3 p.His889Gln Uncertain significance ★ ⚠ same condition
AFF3 p.Lys271Thr 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/aff3-p-glu606fs (accessed [today's date]).

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