Is ASXL1 p.Pro647= (c.1941G>A) pathogenic?

ASXL1 p.Pro647= (c.1941G>A) is classified Likely benign in ASXL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-23). Ultra-rare (popmax 0.0509%, afr); Associated with Inborn genetic diseases.

What condition is associated with ASXL1 p.Pro647= (c.1941G>A)?

ASXL1 p.Pro647= (c.1941G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASXL1 p.Pro647= (c.1941G>A) in the general population?

ASXL1 p.Pro647= (c.1941G>A) is ultra-rare (popmax 0.0509%, afr) (gnomAD).

ASXL1 p.Pro647=

c.1941G>A · rs368131501 · VCV1606532

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0509%, 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 7.5	GERP 1.1, phastCons 1
Overall
CADD	15.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0509% African / African-American · 38/74,620 alleles

Filtering AF 0.0381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0336%

Overall 0.00318% 51/1,604,210 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0509%	1,964
South Asian	0.00332%	30,145
Remaining individualsnot grpmax-eligible	0.00322%	31,033
Finnishnot grpmax-eligible	0.00322%	31,073
European (non-Finnish)	0.000511%	195,874

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: ASXL1
Protein: p.Pro647=
Coding: c.1941G>A
MANE Select: NM_015338
dbSNP: rs368131501
Type: single nucleotide variant
Location: chr20:32434653 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 42.74 · 4 PDB
Residue 647: the 'disordered' region; the 'interaction with ncoa1' region

Full ASXL1 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

ASXL1 p.Pro647Arg Uncertain significance ★ ⚠ same residue
ASXL1 p.Pro647Gln Uncertain significance ★ same residue
ASXL1 p.Pro647Ser Uncertain significance ★ ⚠ same residue
ASXL1 p.Pro647Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ASXL1 p.Pro647Leu Uncertain significance ★ ⚠ same residue
ASXL1 p.Arg1415Ter Pathogenic ★★ same condition
ASXL1 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
ASXL1 p.Ala1002Asp 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/asxl1-p-pro647 (accessed [today's date]).

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