Is ABL1 p.Arg239His (c.716G>A) pathogenic?

ABL1 p.Arg239His (c.716G>A) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.9986); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABL1 p.Arg239His (c.716G>A)?

ABL1 p.Arg239His (c.716G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABL1 p.Arg239His (c.716G>A) in the general population?

ABL1 p.Arg239His (c.716G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ABL1 p.Arg239His (c.716G>A)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

ABL1 p.Arg239His

c.716G>A · rs1391451714 · VCV2604395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 8% in ABL1
REVEL	0.646	pathogenic-leaning
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 10 kb · p 1.5e-16 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,030 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very rare

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: ABL1
Protein: p.Arg239His
Coding: c.716G>A
MANE Select: NM_005157
dbSNP: rs1391451714
Type: single nucleotide variant
Location: chr9:130862929 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 239: an α-helix

Full ABL1 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

ABL1 p.Arg239Cys Uncertain significance ★ ⚠ same residue
ABL1 p.Ala767Val Uncertain significance ★★ ⚠ same condition
ABL1 p.Arg1016His Uncertain significance ★★ ⚠ same condition
ABL1 p.Arg771Gly Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn1088His Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn120Thr Uncertain significance ★★ ⚠ same condition
ABL1 p.Asn414Lys Uncertain significance ★★ ⚠ same condition
ABL1 p.Glu123Gln 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/abl1-p-arg239his (accessed [today's date]).

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