Is MERTK p.Pro862Ser (c.2584C>T) pathogenic?

MERTK p.Pro862Ser (c.2584C>T) is classified Likely benign in MERTK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1289); Rare (popmax 0.224%, afr).

How common is MERTK p.Pro862Ser (c.2584C>T) in the general population?

MERTK p.Pro862Ser (c.2584C>T) is rare (popmax 0.224%, afr) (gnomAD).

What do computational predictors say about MERTK p.Pro862Ser (c.2584C>T)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

MERTK p.Pro862Ser

c.2584C>T · rs143190615 · VCV1140926

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.224%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -14.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	23.6	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 0.224% African / African-American · 168/75,008 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.0112% 181/1,614,110 alleles · rare exomes 87/1,461,846 · genomes 94/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.224%	446
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.005%	20,008
South Asian	0.0022%	45,543
European (non-Finnish)	0.000169%	590,016

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.Pro862Ser
Coding: c.2584C>T
MANE Select: NM_006343
dbSNP: rs143190615
Type: single nucleotide variant
Location: chr2:112028448 (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.Pro862Leu Uncertain significance ★ ⚠ 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-pro862ser (accessed [today's date]).

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