Is LMTK1 p.Ser183Arg (c.549C>G) pathogenic?

LMTK1 p.Ser183Arg (c.549C>G) is classified Uncertain significance in LMTK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.3418); Very rare (popmax 0.000513%, nfe).

How common is LMTK1 p.Ser183Arg (c.549C>G) in the general population?

LMTK1 p.Ser183Arg (c.549C>G) is very rare (popmax 0.000513%, nfe) (gnomAD).

What do computational predictors say about LMTK1 p.Ser183Arg (c.549C>G)?

AlphaMissense predicts ambiguous (score 0.3418) — an in-silico prediction, not a clinical call.

LMTK1 p.Ser183Arg

c.549C>G · rs1454135262 · VCV2215789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000513%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3418	ambiguous
REVEL	0.443	indeterminate
SaProt	LLR -2.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.24, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,139 bp · p 0.00013 · regional, not allelic
Overall
CADD	22.6	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 0.000513% European (non-Finnish) · 6/1,169,856 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000377% 6/1,591,902 alleles · very rare

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: LMTK1
Protein: p.Ser183Arg
Coding: c.549C>G
MANE Select: NM_001080395
dbSNP: rs1454135262
Type: single nucleotide variant
Location: chr17:81127655 (GRCh38)
Gene constraint: LOEUF 1.574 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.54
Residue 183: the protein kinase domain

Full LMTK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LMTK1 p.Ser183Asn Uncertain significance ★ same residue
LMTK1 p.Ala1020Asp Uncertain significance ★ same type
LMTK1 p.Ala1153Ser Uncertain significance ★ same type
LMTK1 p.Ala1191Val Uncertain significance ★ same type
LMTK1 p.Ala1204Val Uncertain significance ★ same type
LMTK1 p.Ala1367Asp Uncertain significance ★ same type
LMTK1 p.Ala1374Ser Uncertain significance ★ same type
LMTK1 p.Ala193Thr Uncertain significance ★ 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/lmtk1-p-ser183arg (accessed [today's date]).

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