Is MERTK p.Pro92Leu (c.275C>T) pathogenic?

MERTK p.Pro92Leu (c.275C>T) is classified Uncertain significance in MERTK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-02). AlphaMissense: likely benign (0.0628); Ultra-rare (popmax 0.0406%, sas); Associated with Inborn genetic diseases.

What condition is associated with MERTK p.Pro92Leu (c.275C>T)?

MERTK p.Pro92Leu (c.275C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MERTK p.Pro92Leu (c.275C>T) in the general population?

MERTK p.Pro92Leu (c.275C>T) is ultra-rare (popmax 0.0406%, sas) (gnomAD).

What do computational predictors say about MERTK p.Pro92Leu (c.275C>T)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

MERTK p.Pro92Leu

c.275C>T · rs200985967 · VCV195264

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.70	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 0.18	GERP 4.1, phastCons 0.003
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	12.02	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 0.0406% South Asian · 37/91,082 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.007% 113/1,614,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0406%	2,462
African / African-American	0.0187%	5,360
Remaining individualsnot grpmax-eligible	0.0064%	15,628
European (non-Finnish)	0.00466%	21,455
Admixed American	0.00333%	30,006
Finnishnot grpmax-eligible	0.00156%	64,032

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.Pro92Leu
Coding: c.275C>T
MANE Select: NM_006343
dbSNP: rs200985967
Type: single nucleotide variant
Location: chr2:111929333 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.78 · 42 PDB
Residue 92: the ig-like c2-type 1 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.Pro92= Likely benign ★ 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-pro92leu (accessed [today's date]).

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