Is AFF3 p.Lys465= (c.1395G>A) pathogenic?

AFF3 p.Lys465= (c.1395G>A) is classified Likely benign in AFF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-16). Absent from gnomAD v4.1; Associated with AFF3-related disorder.

What condition is associated with AFF3 p.Lys465= (c.1395G>A)?

AFF3 p.Lys465= (c.1395G>A) is associated with AFF3-related disorder (ClinVar).

How common is AFF3 p.Lys465= (c.1395G>A) in the general population?

AFF3 p.Lys465= (c.1395G>A) is absent from gnomAD v4.1 (gnomAD).

AFF3 p.Lys465=

c.1395G>A · rs2546113132 · VCV3060909

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

AFF3-related disorder

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 1.1	GERP -1.5, phastCons 1
Overall
CADD	8.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFF3
Protein: p.Lys465=
Coding: c.1395G>A
MANE Select: NM_001386135
dbSNP: rs2546113132
Type: single nucleotide variant
Location: chr2:99594266 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 465: 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.Met238Arg Likely pathogenic ★ ⚠ same condition
AFF3 p.His211Asn Uncertain significance ★ ⚠ same condition
AFF3 p.His889Gln Uncertain significance ★ ⚠ same condition
AFF3 p.Lys271Thr Uncertain significance ★ ⚠ same condition
AFF3 p.Pro332Thr Uncertain significance ★ ⚠ same condition
AFF3 p.Ala203Ser Uncertain significance ⚠ same condition
AFF3 c.2591+5G>A Benign same condition
AFF3 c.922-10C>T Benign 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-lys465 (accessed [today's date]).

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