Is AXL p.Ile708= (c.2124C>T) pathogenic?

AXL p.Ile708= (c.2124C>T) is classified Likely benign in AXL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-19). Ultra-rare (popmax 0.0512%, eas).

How common is AXL p.Ile708= (c.2124C>T) in the general population?

AXL p.Ile708= (c.2124C>T) is ultra-rare (popmax 0.0512%, eas) (gnomAD).

AXL p.Ile708=

c.2124C>T · rs558823493 · VCV1922137

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, eas)

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 -7.3	GERP -3.4
Overall
CADD	5.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% East Asian · 23/44,890 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00186% 30/1,614,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0512%	1,952
South Asian	0.00329%	30,362
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Admixed American	0.00167%	60,018
European (non-Finnish)	8.47e-05%	1,180,034

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.Ile708=
Coding: c.2124C>T
MANE Select: NM_021913
dbSNP: rs558823493
Type: single nucleotide variant
Location: chr19:41256539 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57 · 4 PDB
Residue 708: the protein kinase domain

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

Similar variants

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
AXL c.1286-59G>A 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-ile708 (accessed [today's date]).

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