Is MERTK p.Ala446fs (c.1335_1336del) pathogenic?

MERTK p.Ala446fs (c.13351336del) is classified Pathogenic in MERTK (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-25). Absent from gnomAD; Associated with retinitis pigmentosa 38.

What condition is associated with MERTK p.Ala446fs (c.1335_1336del)?

MERTK p.Ala446fs (c.1335_1336del) is associated with retinitis pigmentosa 38 (ClinVar).

How common is MERTK p.Ala446fs (c.1335_1336del) in the general population?

MERTK p.Ala446fs (c.1335_1336del) is absent from gnomAD (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MERTK p.Ala446fs

c.1335_1336del · rs1676689811 · VCV979013

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

retinitis pigmentosa 38

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.076	GERP 0.68

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Ala446fs
Coding: c.1335_1336del
MANE Select: NM_006343
dbSNP: rs1676689811
Type: Deletion
Location: chr2:111994288 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 446: a UniProt-annotated variant site (in a renal clear cell carcinoma sample; somatic mutation); a β-strand; the fibronectin type-iii 2 domain

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

Disease context

retinitis pigmentosa 38 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

MERTK p.Cys738fs Pathogenic ★★ same condition
MERTK p.Glu792_Ile793insTer Pathogenic ★★ same condition
MERTK p.Gly691fs Pathogenic ★★ same condition
MERTK p.Gly76fs Pathogenic ★★ same condition
MERTK c.56_61+15del Likely pathogenic ★ same condition
MERTK p.Glu808_Tyr810del Likely pathogenic ★ same condition
MERTK c.-8163_c.1145-1213del Pathogenic same condition
MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same condition

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-ala446fs (accessed [today's date]).

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