Is MERTK p.Ser570fs (c.1710_1713del) pathogenic?

MERTK p.Ser570fs (c.17101713del) is classified Pathogenic in MERTK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Very rare (popmax 0.00443%, sas); Associated with inherited retinal dystrophy.

What condition is associated with MERTK p.Ser570fs (c.1710_1713del)?

MERTK p.Ser570fs (c.1710_1713del) is associated with inherited retinal dystrophy (ClinVar).

How common is MERTK p.Ser570fs (c.1710_1713del) in the general population?

MERTK p.Ser570fs (c.1710_1713del) is very rare (popmax 0.00443%, sas) (gnomAD).

MERTK p.Ser570fs

c.1710_1713del · VCV3248842

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00443%, 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 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 1.9, phastCons 1
Overall
CADD	34.0	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 0.00443% South Asian · 4/90,206 alleles

Filtering AF 0.00144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000898%

Overall 0.000318% 5/1,573,430 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00443%	22,552
Remaining individualsnot grpmax-eligible	0.00164%	61,102

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.Ser570fs
Coding: c.1710_1713del
MANE Select: NM_006343
Type: Deletion
Location: chr2:112003109 (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

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

Similar variants

MERTK p.Asn575fs Pathogenic ★★ same condition
MERTK p.Gly76fs Pathogenic ★★ same condition
MERTK p.Ala904_Ser905del Uncertain significance ★★ same condition
MERTK p.Gln413fs Pathogenic ★ same condition
MERTK p.Lys201_Pro203del Likely pathogenic ★ same condition
MERTK p.Ser570Cys Uncertain significance ★ ⚠ same residue
MERTK c.(?_-1 Likely 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-ser570fs (accessed [today's date]).

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