Is LMTK2 p.Asp1426Val (c.4277A>T) pathogenic?

LMTK2 p.Asp1426Val (c.4277A>T) is classified Uncertain significance in LMTK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.18); Very rare (popmax 0.0011%, sas).

How common is LMTK2 p.Asp1426Val (c.4277A>T) in the general population?

LMTK2 p.Asp1426Val (c.4277A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about LMTK2 p.Asp1426Val (c.4277A>T)?

AlphaMissense predicts likely benign (score 0.18) — an in-silico prediction, not a clinical call.

LMTK2 p.Asp1426Val

c.4277A>T · VCV4098762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.18 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.18	likely benign
REVEL	0.451	indeterminate
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.1	GERP 4.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.57 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Overall 6.2e-05% 1/1,614,044 alleles · very rare exomes 1/1,461,834 · genomes 0/152,210 · 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: LMTK2
Protein: p.Asp1426Val
Coding: c.4277A>T
MANE Select: NM_014916
Type: single nucleotide variant
Location: chr7:98203980 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 47.41
Residue 1426: the 'disordered' region

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

Similar variants

LMTK2 p.Asp1426Glu Uncertain significance ★ ⚠ same residue
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

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-asp1426val (accessed [today's date]).

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