Is ABL2 p.Val306Ile (c.916G>A) pathogenic?

ABL2 p.Val306Ile (c.916G>A) is classified Uncertain significance in ABL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely benign (0.0699); Ultra-rare (popmax 0.0134%, eas).

How common is ABL2 p.Val306Ile (c.916G>A) in the general population?

ABL2 p.Val306Ile (c.916G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about ABL2 p.Val306Ile (c.916G>A)?

AlphaMissense predicts likely benign (score 0.0699) — an in-silico prediction, not a clinical call.

ABL2 p.Val306Ile

c.916G>A · VCV3993711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0699 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0699	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.14	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 4.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 21 kb · p 2.9e-22 · regional, not allelic
Overall
CADD	23.2	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 0.0134% East Asian · 6/44,882 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00149% 24/1,614,224 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
African / African-American	0.00666%	15,013
Admixed American	0.005%	20,005
South Asian	0.00329%	30,361
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.Val306Ile
Coding: c.916G>A
MANE Select: NM_007314
Type: single nucleotide variant
Location: chr1:179121639 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.19 · 9 PDB
Residue 306: the protein kinase 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-val306ile (accessed [today's date]).

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