Is LTK p.Val413Ile (c.1237G>A) pathogenic?

LTK p.Val413Ile (c.1237G>A) is classified Likely benign in LTK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely benign (0.0643); Ultra-rare (popmax 0.0165%, mid).

How common is LTK p.Val413Ile (c.1237G>A) in the general population?

LTK p.Val413Ile (c.1237G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about LTK p.Val413Ile (c.1237G>A)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

LTK p.Val413Ile

c.1237G>A · VCV3869021

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.6	GERP -2.6
Regional constraint	o/e 1.07	unconstrained · MANE · 9,710 bp · p 0.011 · regional, not allelic
Overall
CADD	0.866	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 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.0038% 61/1,605,890 alleles · ultra-rare exomes 58/1,453,726 · genomes 3/152,164 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
Finnishnot grpmax-eligible	0.0144%	6,922
Remaining individualsnot grpmax-eligible	0.0113%	8,881
Admixed American	0.00337%	29,643
European (non-Finnish)	0.00332%	30,158
East Asian	0.00224%	44,734
South Asian	0.00222%	45,124

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: LTK
Protein: p.Val413Ile
Coding: c.1237G>A
MANE Select: NM_002344
Type: single nucleotide variant
Location: chr15:41508081 (GRCh38)
Gene constraint: LOEUF 1.42 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.41 · 2 PDB

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

Similar variants

LTK p.Arg569Ser Benign ★★ same type
LTK p.Glu813Ter Likely benign ★★ same type
LTK p.Ala139Thr Uncertain significance ★ ⚠ same type
LTK p.Ala13Thr Uncertain significance ★ ⚠ same type
LTK p.Ala14Ser Uncertain significance ★ ⚠ same type
LTK p.Ala250Val Uncertain significance ★ ⚠ same type
LTK p.Ala305Val Uncertain significance ★ ⚠ same type
LTK p.Ala321Asp 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/ltk-p-val413ile (accessed [today's date]).

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