Is LMTK2 p.Pro91Arg (c.272C>G) pathogenic?

LMTK2 p.Pro91Arg (c.272C>G) is classified Uncertain significance in LMTK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.9778); Absent from gnomAD v4.1.

How common is LMTK2 p.Pro91Arg (c.272C>G) in the general population?

LMTK2 p.Pro91Arg (c.272C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LMTK2 p.Pro91Arg (c.272C>G)?

AlphaMissense predicts likely pathogenic (score 0.9778) — an in-silico prediction, not a clinical call.

LMTK2 p.Pro91Arg

c.272C>G · VCV4047863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9778 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9778	likely pathogenic · top 3% in LMTK2
REVEL	0.509	indeterminate
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 5.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 30 kb · p 0.12 · regional, not allelic
Overall
CADD	27.3	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: LMTK2
Protein: p.Pro91Arg
Coding: c.272C>G
MANE Select: NM_014916
Type: single nucleotide variant
Location: chr7:98141437 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 47.41

Full LMTK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LMTK2 p.Ala1383= Benign ★★ same type
LMTK2 p.Pro1113= Benign ★★ same type
LMTK2 p.Ser910Ile Benign ★★ same type
LMTK2 p.Tyr1032= Benign ★★ same type
LMTK2 p.Ala1155Val Uncertain significance ★ ⚠ same type
LMTK2 p.Ala1183Val Uncertain significance ★ ⚠ same type
LMTK2 p.Ala1242Val Uncertain significance ★ ⚠ same type
LMTK2 p.Ala1284Thr 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/lmtk2-p-pro91arg (accessed [today's date]).

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