Is MERTK p.Gln233Pro (c.698A>C) pathogenic?

MERTK p.Gln233Pro (c.698A>C) is classified Uncertain significance in MERTK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.7494); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with MERTK p.Gln233Pro (c.698A>C)?

MERTK p.Gln233Pro (c.698A>C) is associated with retinitis pigmentosa (ClinVar).

How common is MERTK p.Gln233Pro (c.698A>C) in the general population?

MERTK p.Gln233Pro (c.698A>C) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about MERTK p.Gln233Pro (c.698A>C)?

AlphaMissense predicts likely pathogenic (score 0.7494) — an in-silico prediction, not a clinical call.

MERTK p.Gln233Pro

c.698A>C · VCV3544473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7494 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.7494	likely pathogenic
REVEL	0.099	moderately benign-leaning
SaProt	LLR -14.32	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.21, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MERTK
Protein: p.Gln233Pro
Coding: c.698A>C
MANE Select: NM_006343
Type: single nucleotide variant
Location: chr2:111947508 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 233: 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

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.Gln233= Likely benign ★ 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-gln233pro (accessed [today's date]).

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