Is ABL2 p.Ser466= (c.1398T>G) pathogenic?

ABL2 p.Ser466= (c.1398T>G) is classified Likely benign in ABL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-07). Very rare (popmax 0.000847%, nfe).

How common is ABL2 p.Ser466= (c.1398T>G) in the general population?

ABL2 p.Ser466= (c.1398T>G) is very rare (popmax 0.000847%, nfe) (gnomAD).

ABL2 p.Ser466=

c.1398T>G · rs907046003 · VCV758688

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP -2.9, phastCons 0.91
Overall
CADD	8.643	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,180,022 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)grpmax	0.000847%	118,002

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser466=
Coding: c.1398T>G
MANE Select: NM_007314
dbSNP: rs907046003
Type: single nucleotide variant
Location: chr1:179117342 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.19 · 9 PDB
Residue 466: an α-helix; the protein kinase domain

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-ser466 (accessed [today's date]).

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