Is AFF1 p.Pro532Ser (c.1594C>T) pathogenic?

AFF1 p.Pro532Ser (c.1594C>T) is classified Uncertain significance in AFF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-01). AlphaMissense: likely benign (0.1415); Absent from gnomAD v4.1; Associated with teratoma.

What condition is associated with AFF1 p.Pro532Ser (c.1594C>T)?

AFF1 p.Pro532Ser (c.1594C>T) is associated with teratoma (ClinVar).

How common is AFF1 p.Pro532Ser (c.1594C>T) in the general population?

AFF1 p.Pro532Ser (c.1594C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFF1 p.Pro532Ser (c.1594C>T)?

AlphaMissense predicts likely benign (score 0.1415) — an in-silico prediction, not a clinical call.

AFF1 p.Pro532Ser

c.1594C>T · rs2149766630 · VCV2498269

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1415 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,434)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

teratoma

Computational evidence

Protein change
AlphaMissense	0.1415	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -6.87	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 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 84 kb · p 0.031 · regional, not allelic
Overall
CADD	20.7	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P525S vs ClinVar P532S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,610,434). 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: AFF1
Protein: p.Pro532Ser
Coding: c.1594C>T
MANE Select: NM_001166693
dbSNP: rs2149766630
Type: single nucleotide variant
Location: chr4:87114427 (GRCh38)
Gene constraint: LOEUF 0.49 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 53.06 · 1 PDB
Residue 532: the 'disordered' region

Full AFF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

AFF1 c.1191+8C>T Benign/Likely benign ★★ same type
AFF1 p.Ala40= Benign ★★ same type
AFF1 p.Pro393= Benign ★★ same type
AFF1 p.Ser627Cys Likely benign ★★ ⚠ same type
AFF1 p.Thr426= Likely benign ★★ same type
AFF1 p.Val711Ile Benign ★★ same type
AFF1 p.Ala1047Val Uncertain significance ★ ⚠ same type
AFF1 p.Ala1103Thr Uncertain significance ★ ⚠ same type

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/aff1-p-pro532ser (accessed [today's date]).

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