Is AXL p.Ser202Ala (c.604T>G) pathogenic?

AXL p.Ser202Ala (c.604T>G) is classified Uncertain significance in AXL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0784); Very rare (popmax 0.000932%, nfe).

How common is AXL p.Ser202Ala (c.604T>G) in the general population?

AXL p.Ser202Ala (c.604T>G) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about AXL p.Ser202Ala (c.604T>G)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

AXL p.Ser202Ala

c.604T>G · VCV4188660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -7.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.52 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,914 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,796 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: AXL
Protein: p.Ser202Ala
Coding: c.604T>G
MANE Select: NM_021913
Type: single nucleotide variant
Location: chr19:41230984 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57 · 4 PDB
Residue 202: a disulfide bond; the ig-like c2-type 2 domain; a β-strand

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-ser202ala (accessed [today's date]).

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