Is MERTK p.Asp734= (c.2202C>T) pathogenic?

MERTK p.Asp734= (c.2202C>T) is classified Conflicting classifications of pathogenicity in MERTK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-08-31). Very rare (popmax 0.005%, amr); Associated with retinitis pigmentosa.

What condition is associated with MERTK p.Asp734= (c.2202C>T)?

MERTK p.Asp734= (c.2202C>T) is associated with retinitis pigmentosa (ClinVar).

How common is MERTK p.Asp734= (c.2202C>T) in the general population?

MERTK p.Asp734= (c.2202C>T) is very rare (popmax 0.005%, 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.Asp734=

c.2202C>T · rs1323896467 · VCV893537

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, 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 0.58	GERP -1.2, phastCons 1
Overall
CADD	8.386	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,022 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000342% 5/1,461,110 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,007
European (non-Finnish)	0.00017%	589,939

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.Asp734=
Coding: c.2202C>T
MANE Select: NM_006343
dbSNP: rs1323896467
Type: single nucleotide variant
Location: chr2:112021434 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 734: the protein kinase domain; a turn

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

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.Asp734Val Uncertain significance ★★ ⚠ same residue
MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same condition
MERTK c.2189+1G>T Pathogenic ★★ same condition
MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ same condition
MERTK p.Arg651Ter Pathogenic ★★ same condition
MERTK p.Arg687Ter Pathogenic/Likely pathogenic ★★ same condition
MERTK p.Arg722Ter Pathogenic ★★ same condition
MERTK p.Cys115Trp Pathogenic/Likely 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-asp734 (accessed [today's date]).

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