Is AFF3 p.Ala233Val (c.698C>T) pathogenic?

AFF3 p.Ala233Val (c.698C>T) is classified Pathogenic/Likely pathogenic in AFF3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.9907); Absent from gnomAD v4.1; Associated with KINSSHIP syndrome.

What condition is associated with AFF3 p.Ala233Val (c.698C>T)?

AFF3 p.Ala233Val (c.698C>T) is associated with KINSSHIP syndrome (ClinVar).

How common is AFF3 p.Ala233Val (c.698C>T) in the general population?

AFF3 p.Ala233Val (c.698C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFF3 p.Ala233Val (c.698C>T)?

AlphaMissense predicts likely pathogenic (score 0.9907) — an in-silico prediction, not a clinical call.

AFF3 p.Ala233Val

c.698C>T · rs2104734977 · VCV1077076

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

KINSSHIP syndrome

Computational evidence

Protein change
AlphaMissense	0.9907	likely pathogenic ✓ concordant with ClinVar · top 6% in AFF3
REVEL	0.563	indeterminate
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 35 bp · p 1.9e-05 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFF3
Protein: p.Ala233Val
Coding: c.698C>T
MANE Select: NM_001386135
dbSNP: rs2104734977
Type: single nucleotide variant
Location: chr2:100006807 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 233: the 'disordered' region; a UniProt-annotated variant site (in kins)

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.Ala233Thr Pathogenic ★★ ⚠ same residue
AFF3 p.Ala233Ser Pathogenic ⚠ same residue
AFF3 p.Leu370Phe Uncertain significance ★★ ⚠ same condition
AFF3 p.Ser222Thr Uncertain significance ★★ ⚠ same condition
AFF3 p.Thr808Ala Likely pathogenic ★ ⚠ same condition
AFF3 c.1144-2A>G Uncertain significance ★ same condition
AFF3 c.2466+5G>A Uncertain significance ★ same condition
AFF3 c.53+41939G>A 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/aff3-p-ala233val (accessed [today's date]).

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