Is MERTK p.Gln451= (c.1353A>G) pathogenic?

MERTK p.Gln451= (c.1353A>G) is classified Benign/Likely benign in MERTK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.32%, afr); Associated with retinitis pigmentosa.

What condition is associated with MERTK p.Gln451= (c.1353A>G)?

MERTK p.Gln451= (c.1353A>G) is associated with retinitis pigmentosa (ClinVar).

How common is MERTK p.Gln451= (c.1353A>G) in the general population?

MERTK p.Gln451= (c.1353A>G) is low-frequency (popmax 2.32%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

MERTK p.Gln451=

c.1353A>G · rs35981104 · VCV784993

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.32%, afr)

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 0.67	GERP -3.2, phastCons 0.31
Overall
CADD	2.365	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.32% African / African-American · 1,744/75,040 alleles

Filtering AF 2.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2%

Overall 0.119% 1,928/1,614,184 alleles · low-frequency exomes 968/1,461,880 · genomes 960/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.32%	43
Remaining individualsnot grpmax-eligible	0.168%	595
Admixed American	0.0883%	1,133
Middle Eastern	0.0165%	6,060
South Asian	0.00659%	15,180
European (non-Finnish)	0.00161%	62,107

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.Gln451=
Coding: c.1353A>G
MANE Select: NM_006343
dbSNP: rs35981104
Type: single nucleotide variant
Location: chr2:111994307 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 451: the fibronectin type-iii 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 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
MERTK p.Leu623Ter 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-gln451 (accessed [today's date]).

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