Is AFF2 p.Gly482Arg (c.1444G>A) pathogenic?

AFF2 p.Gly482Arg (c.1444G>A) is classified Uncertain significance in AFF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-27). AlphaMissense: likely benign (0.2367); Very rare (popmax 0.00296%, eas); Associated with Inborn genetic diseases.

What condition is associated with AFF2 p.Gly482Arg (c.1444G>A)?

AFF2 p.Gly482Arg (c.1444G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AFF2 p.Gly482Arg (c.1444G>A) in the general population?

AFF2 p.Gly482Arg (c.1444G>A) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about AFF2 p.Gly482Arg (c.1444G>A)?

AlphaMissense predicts likely benign (score 0.2367) — an in-silico prediction, not a clinical call.

AFF2 p.Gly482Arg

c.1444G>A · rs782182585 · VCV1719842

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2367	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 304 kb · p 0.17 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,841 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000638% 7/1,097,927 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,841
Remaining individualsnot grpmax-eligible	0.0021%	47,627
European (non-Finnish)	0.000558%	179,078

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.Gly482Arg
Coding: c.1444G>A
MANE Select: NM_002025
dbSNP: rs782182585
Type: single nucleotide variant
Location: chrX:148953626 (GRCh38)
Structure: AlphaFold pLDDT 49.27
Residue 482: 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.Gly482Ala 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.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-gly482arg (accessed [today's date]).

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