Is AFF2 p.Tyr288= (c.864C>T) pathogenic?

AFF2 p.Tyr288= (c.864C>T) is classified Likely benign in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). Ultra-rare (popmax 0.0457%, mid).

How common is AFF2 p.Tyr288= (c.864C>T) in the general population?

AFF2 p.Tyr288= (c.864C>T) is ultra-rare (popmax 0.0457%, mid) (gnomAD).

AFF2 p.Tyr288=

c.864C>T · rs782802279 · VCV2661599

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, mid)

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 0.17	GERP -2, phastCons 0.99
Overall
CADD	0.722	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0457% Middle Eastern · 2/4,375 alleles

Filtering AF 0.00809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.00405% 49/1,209,683 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0457%	2,187
Admixed American	0.0109%	9,134
European (non-Finnish)	0.00413%	24,195
South Asian	0.00352%	28,398
African / African-American	0.00351%	28,506
Remaining individualsnot grpmax-eligible	0.0021%	47,582

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.Tyr288=
Coding: c.864C>T
MANE Select: NM_002025
dbSNP: rs782802279
Type: single nucleotide variant
Location: chrX:148662591 (GRCh38)
Structure: AlphaFold pLDDT 49.27

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

Similar variants

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
AFF2 p.Asp187Glu 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-tyr288 (accessed [today's date]).

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