Is LCK p.Cys5= (c.15C>T) pathogenic?

LCK p.Cys5= (c.15C>T) is classified Likely benign in LCK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). Absent from gnomAD v4.1; Associated with severe combined immunodeficiency due to LCK deficiency.

What condition is associated with LCK p.Cys5= (c.15C>T)?

LCK p.Cys5= (c.15C>T) is associated with severe combined immunodeficiency due to LCK deficiency (ClinVar).

How common is LCK p.Cys5= (c.15C>T) in the general population?

LCK p.Cys5= (c.15C>T) is absent from gnomAD v4.1 (gnomAD).

How is Combined immunodeficiency due to LCK deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LCK p.Cys5=

c.15C>T · rs1486428010 · VCV2744098

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

severe combined immunodeficiency due to LCK deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Overall
CADD	15.55	PHRED · no single calibrated threshold — expert panels disagree

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: LCK
Protein: p.Cys5=
Coding: c.15C>T
MANE Select: NM_005356
dbSNP: rs1486428010
Type: single nucleotide variant
Location: chr1:32274344 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 57 PDB
Residue 5: the 'interactions with cd4 and cd8' region

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

Disease context

severe combined immunodeficiency due to LCK deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to LCK deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

LCK p.Cys5Trp Uncertain significance ★ ⚠ same residue
LCK p.Cys5Arg Uncertain significance ★ ⚠ same residue
LCK c.631+3G>A Uncertain significance ★★ same condition
LCK p.Ala284Gly Uncertain significance ★★ ⚠ same condition
LCK p.Arg196Pro Uncertain significance ★★ ⚠ same condition
LCK p.Arg219Gln Uncertain significance ★★ ⚠ same condition
LCK p.Arg222His Uncertain significance ★★ ⚠ same condition
LCK p.Arg461His Uncertain significance ★★ ⚠ same condition

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/lck-p-cys5 (accessed [today's date]).

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