Is MERTK p.Ile930fs (c.2785_2786dup) pathogenic?

MERTK p.Ile930fs (c.27852786dup) is classified Uncertain significance in MERTK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-10-18). Ultra-rare (popmax 0.0283%, amr); Associated with retinitis pigmentosa 38.

What condition is associated with MERTK p.Ile930fs (c.2785_2786dup)?

MERTK p.Ile930fs (c.2785_2786dup) is associated with retinitis pigmentosa 38 (ClinVar).

How common is MERTK p.Ile930fs (c.2785_2786dup) in the general population?

MERTK p.Ile930fs (c.2785_2786dup) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

MERTK p.Ile930fs

c.2785_2786dup · rs773105686 · VCV1425224

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

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	escapes	premature termination codon in the last exon (19 of 19) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -1.4, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 17/59,992 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00483% 78/1,614,068 alleles · ultra-rare exomes 74/1,461,894 · genomes 4/152,174 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,529
Remaining individualsnot grpmax-eligible	0.008%	12,498
European (non-Finnish)	0.00475%	21,072

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.Ile930fs
Coding: c.2785_2786dup
MANE Select: NM_006343
dbSNP: rs773105686
Type: Duplication
Location: chr2:112028648 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB

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.Ile930Leu Uncertain significance ★ ⚠ same residue
MERTK p.Ile930Val Uncertain significance ★ ⚠ same residue
MERTK p.Ser860fs Conflicting classifications of pathogenicity ★ same condition
MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same condition
MERTK c.1605-2A>G Pathogenic ★★ same condition
MERTK c.1867+1G>A Likely pathogenic ★★ same condition
MERTK c.1868-1G>A Pathogenic ★★ same condition
MERTK c.2189+1G>T 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-ile930fs (accessed [today's date]).

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