Is MERTK p.Ile189Val (c.565A>G) pathogenic?

MERTK p.Ile189Val (c.565A>G) is classified Uncertain significance in MERTK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-09). AlphaMissense: likely benign (0.0784); Ultra-rare (popmax 0.068%, afr); Associated with Inborn genetic diseases.

What condition is associated with MERTK p.Ile189Val (c.565A>G)?

MERTK p.Ile189Val (c.565A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MERTK p.Ile189Val (c.565A>G) in the general population?

MERTK p.Ile189Val (c.565A>G) is ultra-rare (popmax 0.068%, afr) (gnomAD).

What do computational predictors say about MERTK p.Ile189Val (c.565A>G)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

MERTK p.Ile189Val

c.565A>G · rs201529080 · VCV935337

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.068%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.68	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 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.068% African / African-American · 51/75,028 alleles

Filtering AF 0.0531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00347% 56/1,613,342 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.068%	1,471
Middle Eastern	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0064%	15,615

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.Ile189Val
Coding: c.565A>G
MANE Select: NM_006343
dbSNP: rs201529080
Type: single nucleotide variant
Location: chr2:111945042 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MERTK p.Ile189Met Uncertain significance ★ ⚠ same residue
MERTK p.Ala29Gly Uncertain significance ★★ ⚠ same condition
MERTK p.Ala353Val Uncertain significance ★★ ⚠ same condition
MERTK p.Ala773Thr Uncertain significance ★★ ⚠ same condition
MERTK p.Ala944Thr Uncertain significance ★★ ⚠ same condition
MERTK p.Arg237Cys Uncertain significance ★★ ⚠ same condition
MERTK p.Arg557Gln Uncertain significance ★★ ⚠ same condition
MERTK p.Arg629Trp Uncertain significance ★★ ⚠ 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-ile189val (accessed [today's date]).

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