Is ABL1 p.Asn146Ser (c.437A>G) pathogenic?

ABL1 p.Asn146Ser (c.437A>G) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: ambiguous (0.3828); Very rare (popmax 0.00133%, afr).

How common is ABL1 p.Asn146Ser (c.437A>G) in the general population?

ABL1 p.Asn146Ser (c.437A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ABL1 p.Asn146Ser (c.437A>G)?

AlphaMissense predicts ambiguous (score 0.3828) — an in-silico prediction, not a clinical call.

ABL1 p.Asn146Ser

c.437A>G · rs774952482 · VCV1450318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.3828	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -5.09	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 903 bp · p 1.4e-15 · regional, not allelic
Overall
CADD	28.4	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

Grpmax group 0.00133% African / African-American · 1/74,932 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,932
South Asian	0.0011%	91,088
European (non-Finnish)	0.000339%	295,009

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: ABL1
Protein: p.Asn146Ser
Coding: c.437A>G
MANE Select: NM_005157
dbSNP: rs774952482
Type: single nucleotide variant
Location: chr9:130854984 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 146: the sh2 domain

Full ABL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABL1 p.Asn146His Uncertain significance ★ ⚠ same residue
ABL1 p.Ala337Thr Pathogenic ★★ ⚠ same type
ABL1 p.Ala433Thr Likely pathogenic ★★ same type
ABL1 p.Asp504Gly Likely pathogenic ★★ ⚠ same type
ABL1 p.Glu509Lys Pathogenic/Likely pathogenic ★★ same type
ABL1 p.Gly254Arg Pathogenic/Likely pathogenic ★★ same type
ABL1 p.Pro230Leu Likely pathogenic ★★ same type
ABL1 p.Trp99Arg Likely pathogenic ★★ 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/abl1-p-asn146ser (accessed [today's date]).

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