Is LMTK1 p.Pro1214Ser (c.3640C>T) pathogenic?

LMTK1 p.Pro1214Ser (c.3640C>T) is classified Uncertain significance in LMTK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.6529); Very rare (popmax 0.00333%, amr).

How common is LMTK1 p.Pro1214Ser (c.3640C>T) in the general population?

LMTK1 p.Pro1214Ser (c.3640C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about LMTK1 p.Pro1214Ser (c.3640C>T)?

AlphaMissense predicts likely pathogenic (score 0.6529) — an in-silico prediction, not a clinical call.

LMTK1 p.Pro1214Ser

c.3640C>T · VCV4635768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6529	likely pathogenic
REVEL	0.274	benign-leaning
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 4,291 bp · p 2.4e-16 · regional, not allelic
Overall
CADD	27.8	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 0.00333% Admixed American · 2/59,986 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000686% 10/1,457,104 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,993
Remaining individualsnot grpmax-eligible	0.0016%	62,356
European (non-Finnish)	0.000594%	168,309

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.Pro1214Ser
Coding: c.3640C>T
MANE Select: NM_001080395
Type: single nucleotide variant
Location: chr17:81120296 (GRCh38)
Gene constraint: LOEUF 1.574 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.54

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

Similar variants

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
LMTK1 p.Ala21Thr 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-pro1214ser (accessed [today's date]).

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