Is AFF3 p.Lys769= (c.2307A>G) pathogenic?

AFF3 p.Lys769= (c.2307A>G) is classified Likely benign in AFF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-06). Rare (popmax 0.459%, eas); Associated with AFF3-related disorder.

What condition is associated with AFF3 p.Lys769= (c.2307A>G)?

AFF3 p.Lys769= (c.2307A>G) is associated with AFF3-related disorder (ClinVar).

How common is AFF3 p.Lys769= (c.2307A>G) in the general population?

AFF3 p.Lys769= (c.2307A>G) is rare (popmax 0.459%, eas) (gnomAD).

AFF3 p.Lys769=

c.2307A>G · rs200425747 · VCV3054555

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.459%, eas)

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 0.5	GERP -0.88, phastCons 1
Overall
CADD	7.495	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.459% East Asian · 206/44,850 alleles

Filtering AF 0.408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.388%

Overall 0.0129% 208/1,613,952 alleles · rare exomes 201/1,461,886 · genomes 7/152,066 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.459%	218
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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.Lys769=
Coding: c.2307A>G
MANE Select: NM_001386135
dbSNP: rs200425747
Type: single nucleotide variant
Location: chr2:99593354 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20

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-lys769 (accessed [today's date]).

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