Is AFF2 p.Lys868del (c.2599AAG[1]) pathogenic?

AFF2 p.Lys868del (c.2599AAG[1]) is classified Uncertain significance in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). Very rare (popmax 0.000447%, nfe).

How common is AFF2 p.Lys868del (c.2599AAG[1]) in the general population?

AFF2 p.Lys868del (c.2599AAG[1]) is very rare (popmax 0.000447%, nfe) (gnomAD).

AFF2 p.Lys868del

c.2599AAG[1] · VCV3900372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Overall
CADD	16.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000447% European (non-Finnish) · 4/895,019 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000331% 4/1,209,635 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: AFF2
Protein: p.Lys868del
Coding: c.2599AAG[1]
MANE Select: NM_002025
Type: Microsatellite
Location: chrX:148958365 (GRCh38)
Structure: AlphaFold pLDDT 49.27

Full AFF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFF2 c.1041+56452_1041+56454del Uncertain significance ★ same type
AFF2 c.-458CGC[6] Uncertain significance ★ same type
AFF2 p.Asn768del Uncertain significance ★ same type
AFF2 c.-458CGC[7] Likely benign ★ same type
AFF2 c.-460GCC[6_25] Pathogenic 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/aff2-p-lys868del (accessed [today's date]).

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