Is AFF3 p.Arg390= (c.1170C>T) pathogenic?

AFF3 p.Arg390= (c.1170C>T) is classified Likely benign in AFF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-10). Ultra-rare (popmax 0.0267%, eas); Associated with AFF3-related disorder.

What condition is associated with AFF3 p.Arg390= (c.1170C>T)?

AFF3 p.Arg390= (c.1170C>T) is associated with AFF3-related disorder (ClinVar).

How common is AFF3 p.Arg390= (c.1170C>T) in the general population?

AFF3 p.Arg390= (c.1170C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

AFF3 p.Arg390=

c.1170C>T · rs768916827 · VCV3057346

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, 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 0.61	GERP -3.6, phastCons 0.045
Overall
CADD	3.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,900 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00192% 31/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,742
Admixed American	0.00667%	15,001
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.00119%	84,286

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.Arg390=
Coding: c.1170C>T
MANE Select: NM_001386135
dbSNP: rs768916827
Type: single nucleotide variant
Location: chr2:99649640 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 390: 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-arg390 (accessed [today's date]).

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