Is AFF2 p.Phe1090= (c.3270C>T) pathogenic?

AFF2 p.Phe1090= (c.3270C>T) is classified Uncertain significance in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-11-30). Ultra-rare (popmax 0.0237%, eas).

How common is AFF2 p.Phe1090= (c.3270C>T) in the general population?

AFF2 p.Phe1090= (c.3270C>T) is ultra-rare (popmax 0.0237%, eas) (gnomAD).

AFF2 p.Phe1090=

c.3270C>T · rs371376716 · VCV194623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.9	GERP -3.8
Overall
CADD	1.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0237% East Asian · 8/33,742 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00852%

Overall 0.00604% 73/1,208,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0237%	4,218
European (non-Finnish)	0.00704%	14,201
Admixed American	0.00219%	45,747
Remaining individualsnot grpmax-eligible	0.0021%	47,539

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.Phe1090=
Coding: c.3270C>T
MANE Select: NM_002025
dbSNP: rs371376716
Type: single nucleotide variant
Location: chrX:148973473 (GRCh38)
Structure: AlphaFold pLDDT 49.27

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

Similar variants

AFF2 p.Phe1090Ile Likely benign ★★ same residue
AFF2 c.3267+5G>C Uncertain significance ★★ same type
AFF2 p.Ala1197Thr Uncertain significance ★★ ⚠ same type
AFF2 p.Ala171Pro Uncertain significance ★★ ⚠ same type
AFF2 p.Arg1238Cys Uncertain significance ★★ ⚠ same type
AFF2 p.Arg1295Cys Uncertain significance ★★ ⚠ same type
AFF2 p.Arg670His Uncertain significance ★★ ⚠ same type
AFF2 p.Asn77Ile Uncertain significance ★★ ⚠ 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-phe1090 (accessed [today's date]).

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