Is ABL2 p.Arg237Cys (c.709C>T) pathogenic?

ABL2 p.Arg237Cys (c.709C>T) is classified Uncertain significance in ABL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: ambiguous (0.3551); Very rare (popmax 0.00669%, eas).

How common is ABL2 p.Arg237Cys (c.709C>T) in the general population?

ABL2 p.Arg237Cys (c.709C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about ABL2 p.Arg237Cys (c.709C>T)?

AlphaMissense predicts ambiguous (score 0.3551) — an in-silico prediction, not a clinical call.

ABL2 p.Arg237Cys

c.709C>T · VCV3792213

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3551 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3551	ambiguous
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -6.74	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 21 kb · p 2.9e-22 · regional, not allelic
Overall
CADD	33.0	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 0.00669% East Asian · 3/44,854 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.0018% 29/1,613,124 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,951
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.00401%	24,913
European (non-Finnish)	0.00161%	62,088
South Asian	0.0011%	91,022

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.Arg237Cys
Coding: c.709C>T
MANE Select: NM_007314
Type: single nucleotide variant
Location: chr1:179121846 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.19 · 9 PDB
Residue 237: the sh2 domain; a β-strand

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-arg237cys (accessed [today's date]).

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