Is AFF3 p.Ala201Pro (c.601G>C) pathogenic?

AFF3 p.Ala201Pro (c.601G>C) is classified Uncertain significance in AFF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0948); Ultra-rare (popmax 0.0446%, eas); Associated with Inborn genetic diseases.

What condition is associated with AFF3 p.Ala201Pro (c.601G>C)?

AFF3 p.Ala201Pro (c.601G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AFF3 p.Ala201Pro (c.601G>C) in the general population?

AFF3 p.Ala201Pro (c.601G>C) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about AFF3 p.Ala201Pro (c.601G>C)?

AlphaMissense predicts likely benign (score 0.0948) — an in-silico prediction, not a clinical call.

AFF3 p.Ala201Pro

c.601G>C · rs199949877 · VCV2612941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0948 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0948	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -1.6, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 2,107 bp · p 0.95 · regional, not allelic
Overall
CADD	18.38	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

Grpmax group 0.0446% East Asian · 20/44,874 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00136% 22/1,614,158 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,244
Remaining individualsnot grpmax-eligible	0.0032%	31,256

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.Ala201Pro
Coding: c.601G>C
MANE Select: NM_001386135
dbSNP: rs199949877
Type: single nucleotide variant
Location: chr2:100006904 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.20
Residue 201: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AFF3 p.Ala233Thr Pathogenic ★★ ⚠ same condition
AFF3 p.Ile1147Asn Uncertain significance ★★ ⚠ same condition
AFF3 p.Leu370Phe Uncertain significance ★★ ⚠ same condition
AFF3 p.Pro321Leu Uncertain significance ★★ ⚠ same condition
AFF3 p.Ser222Thr Uncertain significance ★★ ⚠ same condition
AFF3 p.Thr950Met Uncertain significance ★★ ⚠ same condition
AFF3 p.Ala1100Val Uncertain significance ★ ⚠ same condition
AFF3 p.Ala1103Thr 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-ala201pro (accessed [today's date]).

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