Is AFF4 p.Arg507His (c.1520_1521delinsAT) pathogenic?

AFF4 p.Arg507His (c.15201521delinsAT) is classified Uncertain significance in AFF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-20). Absent from gnomAD; Associated with cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome.

How common is AFF4 p.Arg507His (c.1520_1521delinsAT) in the general population?

AFF4 p.Arg507His (c.1520_1521delinsAT) is absent from gnomAD (gnomAD).

AFF4 p.Arg507His

Q: What condition is associated with AFF4 p.Arg507His (c.1520_1521delinsAT)?

AFF4 p.Arg507His (c.1520_1521delinsAT) is associated with cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome (ClinVar).

c.1520_1521delinsAT · rs2532477251 · VCV1803819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.33	GERP -0.64, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 518 bp · p 0.026 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AFF4
Protein: p.Arg507His
Coding: c.1520_1521delinsAT
MANE Select: NM_014423
dbSNP: rs2532477251
Type: Indel
Location: chr5:132897109 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.62 · 9 PDB
Residue 507: the 'disordered' region

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

Disease context

cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AFF4 p.Arg507Pro Uncertain significance ★ ⚠ same residue
AFF4 p.Arg507= Likely benign ★ same residue
AFF4 p.Arg507Gln Uncertain significance ⚠ same residue
AFF4 p.Arg258Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
AFF4 p.Met260Val Likely pathogenic ★★ ⚠ same condition
AFF4 p.Pro253Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
AFF4 p.Thr254Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
AFF4 c.1133+3A>G 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-arg507his (accessed [today's date]).

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