Is ABL1 p.Phe37Leu (c.111T>A) pathogenic?

ABL1 p.Phe37Leu (c.111T>A) is classified Uncertain significance in ABL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: ambiguous (0.3413); Very rare (popmax 0.00333%, amr).

How common is ABL1 p.Phe37Leu (c.111T>A) in the general population?

ABL1 p.Phe37Leu (c.111T>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ABL1 p.Phe37Leu (c.111T>A)?

AlphaMissense predicts ambiguous (score 0.3413) — an in-silico prediction, not a clinical call.

ABL1 p.Phe37Leu

c.111T>A · VCV3616227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3413	ambiguous
REVEL	0.182	moderately benign-leaning
SaProt	LLR -4.25	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 -1.5	GERP -4
Regional constraint	o/e 0.80	unconstrained · MANE · 19 kb · p 0.078 · regional, not allelic
Overall
CADD	13.36	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 0.00333% Admixed American · 2/59,986 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00131% 2/152,220 alleles · very rare

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.Phe37Leu
Coding: c.111T>A
MANE Select: NM_005157
Type: single nucleotide variant
Location: chr9:130854095 (GRCh38)
Gene constraint: LOEUF 0.19 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 85 PDB
Residue 37: the 'cap' region

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

Similar variants

ABL1 p.Phe37Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ABL1 p.Phe37= Likely benign ★ 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

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-phe37leu (accessed [today's date]).

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