Is LTK p.Ser183Phe (c.548C>T) pathogenic?

LTK p.Ser183Phe (c.548C>T) is classified Uncertain significance in LTK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely benign (0.1676); Rare (popmax 0.193%, eas).

How common is LTK p.Ser183Phe (c.548C>T) in the general population?

LTK p.Ser183Phe (c.548C>T) is rare (popmax 0.193%, eas) (gnomAD).

What do computational predictors say about LTK p.Ser183Phe (c.548C>T)?

AlphaMissense predicts likely benign (score 0.1676) — an in-silico prediction, not a clinical call.

LTK p.Ser183Phe

c.548C>T · rs774659840 · VCV3121495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1676 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.193%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1676	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.5	GERP -0.14, phastCons 0.062
Regional constraint	o/e 1.07	unconstrained · MANE · 9,710 bp · p 0.011 · regional, not allelic
Overall
CADD	22.1	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 0.193% East Asian · 76/39,312 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.00599% 90/1,502,250 alleles · rare exomes 85/1,350,352 · genomes 5/151,898 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.193%	517
South Asian	0.00652%	15,348
Remaining individualsnot grpmax-eligible	0.00172%	58,266
European (non-Finnish)	0.000701%	142,672

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.Ser183Phe
Coding: c.548C>T
MANE Select: NM_002344
dbSNP: rs774659840
Type: single nucleotide variant
Location: chr15:41511926 (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-ser183phe (accessed [today's date]).

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