Is AFF3 p.Gln399= (c.1197G>A) pathogenic?

AFF3 p.Gln399= (c.1197G>A) is classified Likely benign in AFF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-27). Rare (popmax 0.22%, afr); Associated with AFF3-related disorder.

What condition is associated with AFF3 p.Gln399= (c.1197G>A)?

AFF3 p.Gln399= (c.1197G>A) is associated with AFF3-related disorder (ClinVar).

How common is AFF3 p.Gln399= (c.1197G>A) in the general population?

AFF3 p.Gln399= (c.1197G>A) is rare (popmax 0.22%, afr) (gnomAD).

AFF3 p.Gln399=

c.1197G>A · rs149711835 · VCV3048479

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.22%, afr)

Conditions

AFF3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.8	GERP -0.3, phastCons 1
Overall
CADD	16.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.22% African / African-American · 165/74,946 alleles

Filtering AF 0.193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.0109% 174/1,595,578 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.22%	454
Remaining individualsnot grpmax-eligible	0.00967%	10,341
Admixed American	0.0034%	29,375
European (non-Finnish)	8.5e-05%	1,176,260

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.Gln399=
Coding: c.1197G>A
MANE Select: NM_001386135
dbSNP: rs149711835
Type: single nucleotide variant
Location: chr2:99601609 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 399: 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-gln399 (accessed [today's date]).

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