Is MERTK p.Ser371= (c.1113C>T) pathogenic?

MERTK p.Ser371= (c.1113C>T) is classified Conflicting classifications of pathogenicity in MERTK (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-01). Ultra-rare (popmax 0.0165%, mid).

How common is MERTK p.Ser371= (c.1113C>T) in the general population?

MERTK p.Ser371= (c.1113C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

MERTK p.Ser371=

c.1113C>T · rs1676227528 · VCV2083573

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.9	GERP 1.7, phastCons 1
Overall
CADD	13.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00041% 6/1,461,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.00267%	37,511
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000169%	590,002

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.Ser371=
Coding: c.1113C>T
dbSNP: rs1676227528
Type: single nucleotide variant
Location: chr2:111975441 (GRCh38)

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

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-ser371 (accessed [today's date]).

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