Is ASXL2 p.Pro413Ser (c.1237C>T) pathogenic?

ASXL2 p.Pro413Ser (c.1237C>T) is classified Uncertain significance in ASXL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.08); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASXL2 p.Pro413Ser (c.1237C>T)?

ASXL2 p.Pro413Ser (c.1237C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASXL2 p.Pro413Ser (c.1237C>T) in the general population?

ASXL2 p.Pro413Ser (c.1237C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASXL2 p.Pro413Ser (c.1237C>T)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

ASXL2 p.Pro413Ser

c.1237C>T · VCV4160035

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.23	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 4.5	GERP 1.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 5,955 bp · p 0.93 · regional, not allelic
Overall
CADD	13.44	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: ASXL2
Protein: p.Pro413Ser
Coding: c.1237C>T
MANE Select: NM_018263
Type: single nucleotide variant
Location: chr2:25750319 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 47.17 · 1 PDB
Residue 413: the 'disordered' region

Full ASXL2 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

ASXL2 p.Ala1372Gly Uncertain significance ★★ ⚠ same condition
ASXL2 p.Ala682Thr Uncertain significance ★★ ⚠ same condition
ASXL2 p.Arg252Lys Uncertain significance ★★ ⚠ same condition
ASXL2 p.Asn803Lys Uncertain significance ★★ ⚠ same condition
ASXL2 p.Asp1165Glu Uncertain significance ★★ ⚠ same condition
ASXL2 p.Gln1017Glu Uncertain significance ★★ ⚠ same condition
ASXL2 p.Glu363Val Uncertain significance ★★ ⚠ same condition
ASXL2 p.His1092Asn 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/asxl2-p-pro413ser (accessed [today's date]).

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