Is LMTK3 p.Pro495= (c.1485T>C) pathogenic?

LMTK3 p.Pro495= (c.1485T>C) is classified Likely benign in LMTK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). Very rare (popmax 0.00868%, amr).

How common is LMTK3 p.Pro495= (c.1485T>C) in the general population?

LMTK3 p.Pro495= (c.1485T>C) is very rare (popmax 0.00868%, amr) (gnomAD).

LMTK3 p.Pro495=

c.1485T>C · VCV4084818

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00868%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -3.4
Overall
CADD	0.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00868% Admixed American · 4/46,076 alleles

Filtering AF 0.00292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.000262% 4/1,528,226 alleles · very rare exomes 4/1,380,264 · genomes 0/147,962 · joint denominator

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: LMTK3
Protein: p.Pro495=
Coding: c.1485T>C
MANE Select: NM_001388485
Type: single nucleotide variant
Location: chr19:48499584 (GRCh38)
Gene constraint: LOEUF 0.517 · pLI 0.89 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 47.17 · 1 PDB
Residue 495: the 'disordered' region

Full LMTK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LMTK3 p.Leu314= Benign ★★ same type
LMTK3 p.Leu354= Benign ★★ same type
LMTK3 p.Pro22= Likely benign ★★ same type
LMTK3 c.-35G>T Uncertain significance ★ same type
LMTK3 c.-44G>A Uncertain significance ★ same type
LMTK3 c.-45C>T Uncertain significance ★ same type
LMTK3 c.-6G>T Uncertain significance ★ same type
LMTK3 p.Ala1040Asp 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/lmtk3-p-pro495 (accessed [today's date]).

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