Is MERTK p.Arg844Cys (c.2530C>T) pathogenic?

MERTK p.Arg844Cys (c.2530C>T) is classified Pathogenic in MERTK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-31). AlphaMissense: likely pathogenic (0.9631); Ultra-rare (popmax 0.0164%, mid); Associated with MERTK-related disorder.

What condition is associated with MERTK p.Arg844Cys (c.2530C>T)?

MERTK p.Arg844Cys (c.2530C>T) is associated with MERTK-related disorder, retinitis pigmentosa 38, inherited retinal dystrophy (ClinVar).

How common is MERTK p.Arg844Cys (c.2530C>T) in the general population?

MERTK p.Arg844Cys (c.2530C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about MERTK p.Arg844Cys (c.2530C>T)?

AlphaMissense predicts likely pathogenic (score 0.9631) — an in-silico prediction, not a clinical call.

MERTK p.Arg844Cys

c.2530C>T · rs746291728 · VCV801738

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9631 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MERTK-related disorder

Computational evidence

Protein change
AlphaMissense	0.9631	likely pathogenic ✓ concordant with ClinVar · top 7% in MERTK
REVEL	0.794	moderately pathogenic-leaning
SaProt	LLR -12.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000805% 13/1,614,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00223%	44,896
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,080
European (non-Finnish)	0.000763%	131,115

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.Arg844Cys
Coding: c.2530C>T
MANE Select: NM_006343
dbSNP: rs746291728
Type: single nucleotide variant
Location: chr2:112028394 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 844: the protein kinase domain

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

Disease context

MERTK-related disorder

Also linked: retinitis pigmentosa 38 inherited retinal dystrophy

Similar variants

MERTK p.Arg844His Pathogenic ★★ same residue
MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same condition
MERTK c.1605-2A>G Pathogenic ★★ same condition
MERTK c.1787-2A>T Pathogenic/Likely 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

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-arg844cys (accessed [today's date]).

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