Is AFF4 p.Thr973= (c.2919G>A) pathogenic?

AFF4 p.Thr973= (c.2919G>A) is classified Likely benign in AFF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-03). Very rare (popmax 0.00446%, eas); Associated with AFF4-related disorder.

What condition is associated with AFF4 p.Thr973= (c.2919G>A)?

AFF4 p.Thr973= (c.2919G>A) is associated with AFF4-related disorder (ClinVar).

How common is AFF4 p.Thr973= (c.2919G>A) in the general population?

AFF4 p.Thr973= (c.2919G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

AFF4 p.Thr973=

c.2919G>A · rs759710714 · VCV3055124

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -8.6	GERP -11
Overall
CADD	0.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,862 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000744% 12/1,613,058 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,431
South Asian	0.0033%	30,297
Admixed American	0.00167%	59,820
Remaining individualsnot grpmax-eligible	0.0016%	62,452
African / African-American	0.00134%	74,832
European (non-Finnish)	0.000339%	294,944

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.Thr973=
Coding: c.2919G>A
MANE Select: NM_014423
dbSNP: rs759710714
Type: single nucleotide variant
Location: chr5:132887860 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 973: an α-helix

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

Disease context

AFF4-related disorder

Similar variants

AFF4 p.Thr973Arg Uncertain significance ★ ⚠ same residue
AFF4 p.Thr973Met Uncertain significance ★ ⚠ 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

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-thr973 (accessed [today's date]).

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