Is ABL2 p.Arg580Gln (c.1739G>A) pathogenic?

ABL2 p.Arg580Gln (c.1739G>A) is classified Uncertain significance in ABL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.2387); Ultra-rare (popmax 0.0217%, amr).

How common is ABL2 p.Arg580Gln (c.1739G>A) in the general population?

ABL2 p.Arg580Gln (c.1739G>A) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about ABL2 p.Arg580Gln (c.1739G>A)?

AlphaMissense predicts likely benign (score 0.2387) — an in-silico prediction, not a clinical call.

ABL2 p.Arg580Gln

c.1739G>A · rs567232644 · VCV2410935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2387 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2387	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.25	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,725 bp · p 0.85 · regional, not allelic
Overall
CADD	31.0	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 0.0217% Admixed American · 13/60,014 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00161% 26/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,616
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Finnishnot grpmax-eligible	0.00313%	31,997
East Asian	0.00223%	44,878
South Asian	0.0011%	91,086
European (non-Finnish)	0.000593%	168,577

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: ABL2
Protein: p.Arg580Gln
Coding: c.1739G>A
MANE Select: NM_007314
dbSNP: rs567232644
Type: single nucleotide variant
Location: chr1:179110368 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.19 · 9 PDB

Full ABL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABL2 c.*4125A>G Benign ★★ same type
ABL2 p.Lys930Arg Benign ★★ same type
ABL2 p.Thr784Ser Likely benign ★★ same type
ABL2 p.Ala1029Thr Uncertain significance ★ ⚠ same type
ABL2 p.Ala1076Thr Uncertain significance ★ ⚠ same type
ABL2 p.Ala1156Val Uncertain significance ★ ⚠ same type
ABL2 p.Ala38Ser Uncertain significance ★ ⚠ same type
ABL2 p.Ala445Thr Uncertain significance ★ ⚠ 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/abl2-p-arg580gln (accessed [today's date]).

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