Is MERTK p.Pro36Leu (c.107C>T) pathogenic?

MERTK p.Pro36Leu (c.107C>T) is classified Benign/Likely benign in MERTK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0789); Rare (popmax 0.351%, afr).

How common is MERTK p.Pro36Leu (c.107C>T) in the general population?

MERTK p.Pro36Leu (c.107C>T) is rare (popmax 0.351%, afr) (gnomAD).

What do computational predictors say about MERTK p.Pro36Leu (c.107C>T)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

MERTK p.Pro36Leu

c.107C>T · rs150870104 · VCV775751

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.351%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.29	GERP 0.32
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	10.24	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 0.351% African / African-American · 263/75,014 alleles

Filtering AF 0.316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.302%

Overall 0.0197% 318/1,614,146 alleles · rare exomes 149/1,461,890 · genomes 169/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.351%	285
Remaining individualsnot grpmax-eligible	0.0336%	2,977
Admixed American	0.02%	5,002
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00169%	59,001
Finnishnot grpmax-eligible	0.00156%	64,040

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.Pro36Leu
Coding: c.107C>T
MANE Select: NM_006343
dbSNP: rs150870104
Type: single nucleotide variant
Location: chr2:111929165 (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

Similar variants

MERTK p.Pro36= Likely benign ★★ same residue
MERTK c.1296+1G>A Pathogenic/Likely pathogenic ★★ same type
MERTK c.1605-2A>G Pathogenic ★★ same type
MERTK c.1787-2A>T Pathogenic/Likely pathogenic ★★ same type
MERTK c.1867+1G>A Likely pathogenic ★★ same type
MERTK c.1868-1G>A Pathogenic ★★ same type
MERTK c.2189+1G>T Pathogenic ★★ same type
MERTK p.Ala768Thr Pathogenic/Likely pathogenic ★★ same type

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-pro36leu (accessed [today's date]).

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