Is ASXL3 p.Ala1726Val (c.5177C>T) pathogenic?

ASXL3 p.Ala1726Val (c.5177C>T) is classified Uncertain significance in ASXL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0871); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ASXL3 p.Ala1726Val (c.5177C>T)?

ASXL3 p.Ala1726Val (c.5177C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASXL3 p.Ala1726Val (c.5177C>T) in the general population?

ASXL3 p.Ala1726Val (c.5177C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ASXL3 p.Ala1726Val (c.5177C>T)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

ASXL3 p.Ala1726Val

c.5177C>T · VCV4589627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.09	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 0.38	GERP -0.2
Regional constraint	o/e 1.01	unconstrained · MANE · 7,973 bp · p 0.58 · regional, not allelic
Overall
CADD	15.23	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 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,872 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
European (non-Finnish)	0.000339%	294,976

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.Ala1726Val
Coding: c.5177C>T
MANE Select: NM_030632
Type: single nucleotide variant
Location: chr18:33745025 (GRCh38)
Gene constraint: LOEUF 0.229 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.70
Residue 1726: 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

Disease context

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

Similar variants

ASXL3 p.Ala1726Gly Likely benign ★ same residue
ASXL3 p.Arg1068Ter Pathogenic/Likely pathogenic ★★ same condition
ASXL3 p.Arg1444Ter Pathogenic/Likely pathogenic ★★ same condition
ASXL3 p.Ala1529Val Uncertain significance ★★ ⚠ same condition
ASXL3 p.Asn268Ser Uncertain significance ★★ ⚠ same condition
ASXL3 p.Cys2094Tyr Uncertain significance ★★ ⚠ same condition
ASXL3 p.Gln633Leu Uncertain significance ★★ ⚠ same condition
ASXL3 p.Glu854Gln 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/asxl3-p-ala1726val (accessed [today's date]).

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