Is MERTK p.Arg20Ser (c.60A>T) pathogenic?

MERTK p.Arg20Ser (c.60A>T) is classified Conflicting classifications of pathogenicity in MERTK (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1178); Common (popmax 7.52%, mid) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with MERTK p.Arg20Ser (c.60A>T)?

MERTK p.Arg20Ser (c.60A>T) is associated with retinitis pigmentosa, retinitis pigmentosa 38 (ClinVar).

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.Arg20Ser (c.60A>T)?

AlphaMissense predicts likely benign (score 0.1178) — an in-silico prediction, not a clinical call.

MERTK p.Arg20Ser

Q: How common is MERTK p.Arg20Ser (c.60A>T) in the general population?

MERTK p.Arg20Ser (c.60A>T) is common (popmax 7.52%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.60A>T · rs35898499 · VCV95372

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1178 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.52%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.1178	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -2, phastCons 0.98
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	14.73	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 7.52% Middle Eastern · 448/5,958 alleles

Filtering AF 6.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.72%

Overall 4.06% 64,669/1,591,892 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	12.2%	8
Middle Easterngrpmax	7.52%	13
Amishnot grpmax-eligible	5.59%	18
Remaining individualsnot grpmax-eligible	4.52%	22
European (non-Finnish)	4.5%	22
Finnishnot grpmax-eligible	2.88%	35
Admixed American	2.65%	38
South Asian	1.47%	68
African / African-American	0.773%	129
East Asian	0.0137%	7,311

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg20Ser
Coding: c.60A>T
MANE Select: NM_006343
dbSNP: rs35898499
Type: single nucleotide variant
Location: chr2:111898795 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 20: a UniProt-annotated variant site (in)

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

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.Arg20Thr Uncertain significance ★ ⚠ same residue
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

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-arg20ser (accessed [today's date]).

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