Is ASXL2 p.Pro140= (c.420G>A) pathogenic?

ASXL2 p.Pro140= (c.420G>A) is classified Benign/Likely benign in ASXL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-25). Ultra-rare (popmax 0.09%, afr); Associated with Inborn genetic diseases.

What condition is associated with ASXL2 p.Pro140= (c.420G>A)?

ASXL2 p.Pro140= (c.420G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASXL2 p.Pro140= (c.420G>A) in the general population?

ASXL2 p.Pro140= (c.420G>A) is ultra-rare (popmax 0.09%, afr) (gnomAD).

ASXL2 p.Pro140=

c.420G>A · rs145820534 · VCV1640032

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.027	GERP -3.3, phastCons 0.18
Overall
CADD	5.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.09% African / African-American · 67/74,470 alleles

Filtering AF 0.0726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0664%

Overall 0.00651% 105/1,611,790 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.09%	1,111
Remaining individualsnot grpmax-eligible	0.00801%	12,488
East Asian	0.00669%	14,941
Admixed American	0.00503%	19,895
Finnishnot grpmax-eligible	0.00469%	21,301
European (non-Finnish)	0.00195%	51,264
South Asian	0.0011%	90,866

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: ASXL2
Protein: p.Pro140=
Coding: c.420G>A
MANE Select: NM_018263
dbSNP: rs145820534
Type: single nucleotide variant
Location: chr2:25771524 (GRCh38)
Gene constraint: LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 47.17 · 1 PDB
Residue 140: 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.Pro140Ala Uncertain significance ★ ⚠ same residue
ASXL2 p.Pro140Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro140 (accessed [today's date]).

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