Is MERTK p.Pro149fs (c.444dup) pathogenic?

MERTK p.Pro149fs (c.444dup) is classified Pathogenic in MERTK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-27). Very rare (popmax 0.0011%, sas); Associated with inherited retinal dystrophy.

What condition is associated with MERTK p.Pro149fs (c.444dup)?

MERTK p.Pro149fs (c.444dup) is associated with inherited retinal dystrophy (ClinVar).

How common is MERTK p.Pro149fs (c.444dup) in the general population?

MERTK p.Pro149fs (c.444dup) is very rare (popmax 0.0011%, sas) (gnomAD).

MERTK p.Pro149fs

c.444dup · VCV3381808

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

inherited retinal dystrophy

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 2 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 6.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,038 alleles

Overall 6.84e-05% 1/1,461,688 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: MERTK
Protein: p.Pro149fs
Coding: c.444dup
MANE Select: NM_006343
Type: Duplication
Location: chr2:111929501 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 149: a disulfide bond; the ig-like c2-type 1 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MERTK c.2189+1G>T Pathogenic ★★ same condition
MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ same condition
MERTK p.Arg651Ter Pathogenic ★★ same condition
MERTK p.Arg722Ter Pathogenic ★★ same condition
MERTK p.Arg727Ter Pathogenic ★★ same condition
MERTK p.Arg732Ter Pathogenic ★★ same condition
MERTK p.Arg775Ter Pathogenic ★★ same condition
MERTK p.Arg844Cys 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-pro149fs (accessed [today's date]).

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