Is AFF3 p.Asp598fs (c.1788del) pathogenic?

AFF3 p.Asp598fs (c.1788del) is classified Benign in AFF3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-05-04). Common (popmax 18.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with KINSSHIP syndrome.

What condition is associated with AFF3 p.Asp598fs (c.1788del)?

AFF3 p.Asp598fs (c.1788del) is associated with KINSSHIP syndrome (ClinVar).

AFF3 p.Asp598fs

Q: How common is AFF3 p.Asp598fs (c.1788del) in the general population?

AFF3 p.Asp598fs (c.1788del) is common (popmax 18.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1788del · rs201754690 · VCV3059499

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Common

common (popmax 18.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

KINSSHIP syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 15 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.74	GERP 0.38
Overall
CADD	12.56	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.1% East Asian · 7,836/43,306 alleles

Filtering AF 17.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.6%

Overall 5.41% 84,142/1,556,080 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	18.1%	6
Middle Eastern	6.42%	16
Remaining individualsnot grpmax-eligible	6.1%	16
European (non-Finnish)	5.4%	19
South Asian	4.88%	21
Admixed American	4.37%	23
Ashkenazi Jewishnot grpmax-eligible	3.65%	27
Finnishnot grpmax-eligible	2.98%	34
African / African-American	1.21%	83
Amishnot grpmax-eligible	0.11%	910

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: AFF3
Protein: p.Asp598fs
Coding: c.1788del
MANE Select: NM_001386135
dbSNP: rs201754690
Type: Deletion
Location: chr2:99593873 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 598: the 'disordered' region

Full AFF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KINSSHIP syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AFF3 p.Ser517fs Likely pathogenic ★ same condition
AFF3 p.Asp598Tyr Uncertain significance ★ ⚠ same residue
AFF3 p.Ala233Thr Pathogenic ★★ ⚠ same condition
AFF3 p.Ala233Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
AFF3 p.Leu370Phe Uncertain significance ★★ ⚠ same condition
AFF3 p.Ser222Thr Uncertain significance ★★ ⚠ same condition
AFF3 p.Pro231Arg Pathogenic ★ same condition
AFF3 p.Thr808Ala Likely pathogenic ★ ⚠ 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/aff3-p-asp598fs (accessed [today's date]).

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