Is AFF2 p.Leu591= (c.1773C>T) pathogenic?

AFF2 p.Leu591= (c.1773C>T) is classified Likely benign in AFF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-23). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AFF2 p.Leu591= (c.1773C>T)?

AFF2 p.Leu591= (c.1773C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AFF2 p.Leu591= (c.1773C>T) in the general population?

AFF2 p.Leu591= (c.1773C>T) is absent from gnomAD v4.1 (gnomAD).

AFF2 p.Leu591=

c.1773C>T · rs2521891502 · VCV1779831

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

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 0.2	GERP -2, phastCons 0.97
Overall
CADD	2.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFF2
Protein: p.Leu591=
Coding: c.1773C>T
MANE Select: NM_002025
dbSNP: rs2521891502
Type: single nucleotide variant
Location: chrX:148955818 (GRCh38)
Structure: AlphaFold pLDDT 49.27
Residue 591: the 'disordered' region

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.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
AFF2 p.His366Arg 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-leu591 (accessed [today's date]).

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