Is AXL p.Thr239= (c.717G>A) pathogenic?

AXL p.Thr239= (c.717G>A) is classified Likely benign in AXL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Ultra-rare (popmax 0.0134%, eas).

How common is AXL p.Thr239= (c.717G>A) in the general population?

AXL p.Thr239= (c.717G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

AXL p.Thr239=

c.717G>A · rs142452494 · VCV2713488

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -11	GERP -2.7
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,898 alleles

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

Overall 0.00198% 32/1,613,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,917
East Asiangrpmax	0.0134%	7,483
African / African-American	0.00935%	10,697
South Asian	0.0022%	45,535
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.000932%	107,259

Ashkenazi Jewish 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: AXL
Protein: p.Thr239=
Coding: c.717G>A
MANE Select: NM_021913
dbSNP: rs142452494
Type: single nucleotide variant
Location: chr19:41231232 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57 · 4 PDB
Residue 239: the fibronectin type-iii 1 domain

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

Similar variants

AXL p.Thr239Met Uncertain significance ★ ⚠ same residue
AXL p.Arg217His Uncertain significance ★★ ⚠ same type
AXL p.Glu818Lys Uncertain significance ★★ same type
AXL p.Pro833Arg Uncertain significance ★★ ⚠ same type
AXL c.1135-238C>T Benign ★★ same type
AXL c.1285+62C>G Benign ★★ same type
AXL c.1286-159G>A Benign ★★ same type
AXL c.1286-185C>T Benign ★★ 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/axl-p-thr239 (accessed [today's date]).

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