Is MERTK p.Ser52fs (c.154del) pathogenic?

MERTK p.Ser52fs (c.154del) is classified Pathogenic in MERTK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). Very rare (popmax 0.00267%, afr).

How common is MERTK p.Ser52fs (c.154del) in the general population?

MERTK p.Ser52fs (c.154del) is very rare (popmax 0.00267%, afr) (gnomAD).

MERTK p.Ser52fs

c.154del · rs1371550108 · VCV1075717

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 -0.11	GERP -8.7, phastCons 0.001
Overall
CADD	19.5	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 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,048 alleles · very rare exomes 0/1,461,878 · genomes 2/152,170 · joint denominator

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.Ser52fs
Coding: c.154del
MANE Select: NM_006343
dbSNP: rs1371550108
Type: Deletion
Location: chr2:111929212 (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

Similar variants

MERTK p.Arg755fs Pathogenic/Likely pathogenic ★★ same type
MERTK p.Asn575fs Pathogenic ★★ same type
MERTK p.Asp169fs Pathogenic ★★ same type
MERTK p.Cys738fs Pathogenic ★★ same type
MERTK p.Glu792_Ile793insTer Pathogenic ★★ same type
MERTK p.Gly691fs Pathogenic ★★ same type
MERTK p.Gly76fs Pathogenic ★★ same type
MERTK p.Ala904_Ser905del 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-ser52fs (accessed [today's date]).

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