Is MERTK p.Pro252= (c.756A>G) pathogenic?

MERTK p.Pro252= (c.756A>G) is classified Benign/Likely benign in MERTK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Low-frequency (popmax 4.35%, amr); Associated with retinitis pigmentosa.

What condition is associated with MERTK p.Pro252= (c.756A>G)?

MERTK p.Pro252= (c.756A>G) is associated with retinitis pigmentosa, retinitis pigmentosa 38, inherited retinal dystrophy (ClinVar).

How common is MERTK p.Pro252= (c.756A>G) in the general population?

MERTK p.Pro252= (c.756A>G) is low-frequency (popmax 4.35%, 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.Pro252=

c.756A>G · rs3761702 · VCV330745

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.35%, amr)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4.8
Overall
CADD	0.743	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.35% Admixed American · 2,610/60,022 alleles

Filtering AF 4.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.15%

Overall 0.585% 9,435/1,613,988 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	4.35%	23
African / African-American	4.23%	24
East Asian	2.22%	45
Ashkenazi Jewishnot grpmax-eligible	1.24%	81
Remaining individualsnot grpmax-eligible	0.663%	151
Middle Eastern	0.285%	351
South Asian	0.271%	369
Finnishnot grpmax-eligible	0.133%	753
European (non-Finnish)	0.129%	773

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.Pro252=
Coding: c.756A>G
MANE Select: NM_006343
dbSNP: rs3761702
Type: single nucleotide variant
Location: chr2:111947566 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 252: a disulfide bond; the ig-like c2-type 2 domain

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

Disease context

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

Also linked: retinitis pigmentosa 38 inherited retinal dystrophy

For Retinitis pigmentosa (Orphanet):

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

Similar variants

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
MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ same condition
MERTK p.Ala768Val Likely pathogenic ★★ same condition
MERTK p.Arg651Ter 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-pro252 (accessed [today's date]).

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