Is ASXL3 p.Pro2037= (c.6111A>C) pathogenic?

ASXL3 p.Pro2037= (c.6111A>C) is classified Likely benign in ASXL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). Ultra-rare (popmax 0.0126%, afr).

How common is ASXL3 p.Pro2037= (c.6111A>C) in the general population?

ASXL3 p.Pro2037= (c.6111A>C) is ultra-rare (popmax 0.0126%, afr) (gnomAD).

ASXL3 p.Pro2037=

c.6111A>C · VCV3898177

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, afr)

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 -4.4	GERP -2.8
Overall
CADD	0.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0126% African / African-American · 1/7,908 alleles

Overall 0.00191% 6/314,306 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0325%	3,077
African / African-Americangrpmax	0.0126%	7,908
Remaining individualsnot grpmax-eligible	0.00929%	10,766
European (non-Finnish)	0.000398%	251,346

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASXL3
Protein: p.Pro2037=
Coding: c.6111A>C
MANE Select: NM_030632
Type: single nucleotide variant
Location: chr18:33745959 (GRCh38)
Gene constraint: LOEUF 0.229 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.70
Residue 2037: the 'disordered' region; a UniProt-annotated variant site (found in a patient with cohesinopathy; uncertain significance)

Full ASXL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASXL3 p.Pro2037Ala Uncertain significance ★ ⚠ same residue
ASXL3 p.Pro2037Gln Likely benign ★ ⚠ same residue
ASXL3 p.Pro2037Leu Uncertain significance ⚠ same residue
ASXL3 p.Pro2037fs Conflicting classifications of pathogenicity ★ ⚠ same residue
ASXL3 c.3039+1G>A Pathogenic ★★ same type
ASXL3 p.Arg1036Ter Pathogenic/Likely pathogenic ★★ same type
ASXL3 p.Arg1068Ter Pathogenic/Likely pathogenic ★★ same type
ASXL3 p.Arg1117Ter Pathogenic/Likely pathogenic ★★ 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/asxl3-p-pro2037 (accessed [today's date]).

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