Is AFF3 p.Pro332Thr (c.994C>A) pathogenic?

AFF3 p.Pro332Thr (c.994C>A) is classified Uncertain significance in AFF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-13). AlphaMissense: likely benign (0.0891); Absent from gnomAD v4.1; Associated with AFF3-related disorder.

What condition is associated with AFF3 p.Pro332Thr (c.994C>A)?

AFF3 p.Pro332Thr (c.994C>A) is associated with AFF3-related disorder (ClinVar).

How common is AFF3 p.Pro332Thr (c.994C>A) in the general population?

AFF3 p.Pro332Thr (c.994C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFF3 p.Pro332Thr (c.994C>A)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

AFF3 p.Pro332Thr

c.994C>A · rs770911611 · VCV2630082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

AFF3-related disorder

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.323	indeterminate
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 413 kb · p 0.58 · regional, not allelic
Overall
CADD	19.81	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Pro332Thr
Coding: c.994C>A
MANE Select: NM_001386135
dbSNP: rs770911611
Type: single nucleotide variant
Location: chr2:99752229 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 332: the 'disordered' region

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

Disease context

AFF3-related disorder

Similar variants

AFF3 p.Met238Arg Likely pathogenic ★ ⚠ same condition
AFF3 p.His211Asn Uncertain significance ★ ⚠ same condition
AFF3 p.His889Gln Uncertain significance ★ ⚠ same condition
AFF3 p.Lys271Thr Uncertain significance ★ ⚠ same condition
AFF3 p.Ala203Ser Uncertain significance ⚠ same condition
AFF3 c.2591+5G>A Benign same condition
AFF3 c.922-10C>T Benign same condition
AFF3 p.Arg390= Likely benign 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-pro332thr (accessed [today's date]).

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