Is AFF4 p.Thr784= (c.2352G>A) pathogenic?

AFF4 p.Thr784= (c.2352G>A) is classified Likely benign in AFF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-15). Very rare (popmax 0.00988%, sas); Associated with AFF4-related disorder.

What condition is associated with AFF4 p.Thr784= (c.2352G>A)?

AFF4 p.Thr784= (c.2352G>A) is associated with AFF4-related disorder (ClinVar).

How common is AFF4 p.Thr784= (c.2352G>A) in the general population?

AFF4 p.Thr784= (c.2352G>A) is very rare (popmax 0.00988%, sas) (gnomAD).

AFF4 p.Thr784=

c.2352G>A · rs569024443 · VCV3053652

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

AFF4-related disorder

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 -6.5	GERP -11
Overall
CADD	1.416	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,086 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00167% 27/1,614,084 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,121
African / African-American	0.004%	25,011
East Asian	0.00223%	44,874
Admixed American	0.00167%	60,010
European (non-Finnish)	0.0011%	90,768

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: AFF4
Protein: p.Thr784=
Coding: c.2352G>A
MANE Select: NM_014423
dbSNP: rs569024443
Type: single nucleotide variant
Location: chr5:132893074 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 784: the 'disordered' region

Full AFF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AFF4-related disorder

Similar variants

AFF4 p.Thr784Met Conflicting classifications of pathogenicity ★ ⚠ same residue
AFF4 p.Glu657Asp Uncertain significance ★★ ⚠ same condition
AFF4 p.Ser839Cys Uncertain significance ★★ ⚠ same condition
AFF4 p.Ala551Thr Uncertain significance ★ ⚠ same condition
AFF4 p.Arg209Ser Uncertain significance ★ ⚠ same condition
AFF4 p.Arg725Lys Uncertain significance ★ ⚠ same condition
AFF4 p.Asp422Gly Uncertain significance ★ ⚠ same condition
AFF4 p.Pro611Leu 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/aff4-p-thr784 (accessed [today's date]).

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