Is MERTK p.Arg466Glu (c.1396_1397delinsGA) pathogenic?

MERTK p.Arg466Glu (c.13961397delinsGA) is classified Uncertain significance in MERTK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). Absent from gnomAD.

How common is MERTK p.Arg466Glu (c.1396_1397delinsGA) in the general population?

MERTK p.Arg466Glu (c.1396_1397delinsGA) is absent from gnomAD (gnomAD).

MERTK p.Arg466Glu

c.1396_1397delinsGA · rs386649210 · VCV1414697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 0.58, phastCons 0.89
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MERTK
Protein: p.Arg466Glu
Coding: c.1396_1397delinsGA
MANE Select: NM_006343
dbSNP: rs386649210
Type: Indel
Location: chr2:111994350 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 466: a UniProt-annotated variant site (in); a β-strand; the fibronectin type-iii 2 domain

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

Similar variants

MERTK p.Arg466Lys Benign ★★ same residue
MERTK p.Arg466Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
MERTK c.1689_1690+5delinsATATTA Pathogenic ★ same type
MERTK p.Cys218Gly Uncertain significance ★ 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/mertk-p-arg466glu (accessed [today's date]).

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