Is ABL2 p.Lys280Gln (c.838A>C) pathogenic?

ABL2 p.Lys280Gln (c.838A>C) is classified Uncertain significance in ABL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: ambiguous (0.4005); Absent from gnomAD v4.1.

How common is ABL2 p.Lys280Gln (c.838A>C) in the general population?

ABL2 p.Lys280Gln (c.838A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABL2 p.Lys280Gln (c.838A>C)?

AlphaMissense predicts ambiguous (score 0.4005) — an in-silico prediction, not a clinical call.

ABL2 p.Lys280Gln

c.838A>C · VCV4636397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4005 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4005	ambiguous
REVEL	0.159	moderately benign-leaning
SaProt	LLR -5.54	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 21 kb · p 2.9e-22 · regional, not allelic
Overall
CADD	27.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABL2
Protein: p.Lys280Gln
Coding: c.838A>C
MANE Select: NM_007314
Type: single nucleotide variant
Location: chr1:179121717 (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-lys280gln (accessed [today's date]).

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