Is MERTK p.Lys552Met (c.1655A>T) pathogenic?

MERTK p.Lys552Met (c.1655A>T) is classified Uncertain significance in MERTK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-19). AlphaMissense: ambiguous (0.3663); Absent from gnomAD v4.1.

How common is MERTK p.Lys552Met (c.1655A>T) in the general population?

MERTK p.Lys552Met (c.1655A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MERTK p.Lys552Met (c.1655A>T)?

AlphaMissense predicts ambiguous (score 0.3663) — an in-silico prediction, not a clinical call.

MERTK p.Lys552Met

c.1655A>T · rs2104405157 · VCV1387946

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3663	ambiguous
REVEL	0.454	indeterminate
SaProt	LLR -8.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP -0.47, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 130 kb · p 0.00043 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MERTK
Protein: p.Lys552Met
Coding: c.1655A>T
MANE Select: NM_006343
dbSNP: rs2104405157
Type: single nucleotide variant
Location: chr2:112001251 (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.Lys552Arg 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-lys552met (accessed [today's date]).

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