Is MERTK p.Ser627= (c.1881A>G) pathogenic?

MERTK p.Ser627= (c.1881A>G) is classified Benign in MERTK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 62.1%, amr) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with MERTK p.Ser627= (c.1881A>G)?

MERTK p.Ser627= (c.1881A>G) is associated with inherited retinal dystrophy, retinitis pigmentosa 38, retinitis pigmentosa (ClinVar).

MERTK p.Ser627=

Q: How common is MERTK p.Ser627= (c.1881A>G) in the general population?

MERTK p.Ser627= (c.1881A>G) is common (popmax 62.1%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1881A>G · rs1131244 · VCV330762

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 62.1%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

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 -12	GERP -3.7
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 62.1% Admixed American · 37,270/59,974 alleles

Filtering AF 61.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 61.8%

Overall 60.3% 972,042/1,611,140 alleles · common exomes 884,618/1,459,248 · genomes 87,424/151,892 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	66.7%	1
Ashkenazi Jewishnot grpmax-eligible	63.6%	2
Admixed Americangrpmax	62.1%	2
European (non-Finnish)	62%	2
Middle Eastern	61.1%	2
Remaining individualsnot grpmax-eligible	60%	2
South Asian	58.1%	2
African / African-American	51%	2
Amishnot grpmax-eligible	49.9%	2
East Asian	24.3%	4

Finnish 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.Ser627=
Coding: c.1881A>G
MANE Select: NM_006343
dbSNP: rs1131244
Type: single nucleotide variant
Location: chr2:112008396 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 627: the protein kinase domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 38 retinitis pigmentosa

Similar variants

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
MERTK p.Arg651Ter 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-ser627 (accessed [today's date]).

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