Is MERTK p.His807Arg (c.2420A>G) pathogenic?

MERTK p.His807Arg (c.2420A>G) is classified Uncertain significance in MERTK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely pathogenic (0.7528); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with MERTK p.His807Arg (c.2420A>G)?

MERTK p.His807Arg (c.2420A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MERTK p.His807Arg (c.2420A>G) in the general population?

MERTK p.His807Arg (c.2420A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about MERTK p.His807Arg (c.2420A>G)?

AlphaMissense predicts likely pathogenic (score 0.7528) — an in-silico prediction, not a clinical call.

MERTK p.His807Arg

c.2420A>G · VCV3294268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7528 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7528	likely pathogenic
REVEL	0.723	pathogenic-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 0.53, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	26.2	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 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000479% 7/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
European (non-Finnish)	0.000424%	236,008

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.His807Arg
Coding: c.2420A>G
MANE Select: NM_006343
Type: single nucleotide variant
Location: chr2:112022328 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 807: an α-helix; the protein kinase domain

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.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
MERTK p.Arg796Gln 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-his807arg (accessed [today's date]).

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