Is AXL p.Ser734= (c.2202C>T) pathogenic?

AXL p.Ser734= (c.2202C>T) is classified Likely benign in AXL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-21). Ultra-rare (popmax 0.0617%, amr).

How common is AXL p.Ser734= (c.2202C>T) in the general population?

AXL p.Ser734= (c.2202C>T) is ultra-rare (popmax 0.0617%, amr) (gnomAD).

AXL p.Ser734=

c.2202C>T · VCV3670942

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, amr)

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 0.54	GERP -3.4, phastCons 1
Overall
CADD	9.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0617% Admixed American · 37/59,978 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0405%

Overall 0.00235% 38/1,614,006 alleles · ultra-rare exomes 36/1,461,878 · genomes 2/152,128 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0617%	1,621
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Ser734=
Coding: c.2202C>T
MANE Select: NM_021913
Type: single nucleotide variant
Location: chr19:41257498 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57 · 4 PDB
Residue 734: the protein kinase domain; an α-helix

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-ser734 (accessed [today's date]).

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