Is AFF2 p.Phe1090Ile (c.3268T>A) pathogenic?

AFF2 p.Phe1090Ile (c.3268T>A) is classified Likely benign in AFF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-07-07). AlphaMissense: ambiguous (0.3942); Ultra-rare (popmax 0.0771%, afr); Associated with Inborn genetic diseases.

What condition is associated with AFF2 p.Phe1090Ile (c.3268T>A)?

AFF2 p.Phe1090Ile (c.3268T>A) is associated with Inborn genetic diseases (ClinVar).

How common is AFF2 p.Phe1090Ile (c.3268T>A) in the general population?

AFF2 p.Phe1090Ile (c.3268T>A) is ultra-rare (popmax 0.0771%, afr) (gnomAD).

What do computational predictors say about AFF2 p.Phe1090Ile (c.3268T>A)?

AlphaMissense predicts ambiguous (score 0.3942) — an in-silico prediction, not a clinical call.

AFF2 p.Phe1090Ile

c.3268T>A · rs147991137 · VCV760908

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3942 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0771%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3942	ambiguous
REVEL	0.087	moderately benign-leaning
SaProt	LLR -3.17	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.76, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 14 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0771% African / African-American · 44/57,075 alleles

Filtering AF 0.059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0526%

Overall 0.00413% 50/1,209,373 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0771%	1,297
Remaining individualsnot grpmax-eligible	0.00841%	11,888
Admixed American	0.00437%	22,898

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.Phe1090Ile
Coding: c.3268T>A
MANE Select: NM_002025
dbSNP: rs147991137
Type: single nucleotide variant
Location: chrX:148973471 (GRCh38)
Structure: AlphaFold pLDDT 49.27

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AFF2 p.Phe1090= Uncertain significance ★ same residue
AFF2 p.Ala1197Thr Uncertain significance ★★ ⚠ same condition
AFF2 p.Arg1295Cys Uncertain significance ★★ ⚠ same condition
AFF2 p.Asp187Glu Uncertain significance ★★ ⚠ same condition
AFF2 p.Gln205Lys Uncertain significance ★★ ⚠ same condition
AFF2 p.Gly482Arg Uncertain significance ★★ ⚠ same condition
AFF2 p.Gly740Val Uncertain significance ★★ ⚠ same condition
AFF2 p.His1070Arg Uncertain significance ★★ ⚠ 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/aff2-p-phe1090ile (accessed [today's date]).

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