Is LCK p.Asp283= (c.849C>T) pathogenic?

LCK p.Asp283= (c.849C>T) is classified Likely benign in LCK (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-23). Very rare (popmax 0.00659%, sas); Associated with severe combined immunodeficiency due to LCK deficiency.

What condition is associated with LCK p.Asp283= (c.849C>T)?

LCK p.Asp283= (c.849C>T) is associated with severe combined immunodeficiency due to LCK deficiency (ClinVar).

How common is LCK p.Asp283= (c.849C>T) in the general population?

LCK p.Asp283= (c.849C>T) is very rare (popmax 0.00659%, sas) (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.Asp283=

c.849C>T · rs760860694 · VCV1134626

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

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 -4.1	GERP -5.6
Overall
CADD	8.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,070 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000547% 8/1,461,814 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,178
Remaining individualsnot grpmax-eligible	0.0032%	31,248

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: LCK
Protein: p.Asp283=
Coding: c.849C>T
MANE Select: NM_005356
dbSNP: rs760860694
Type: single nucleotide variant
Location: chr1:32276671 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 57 PDB
Residue 283: the protein kinase domain; an α-helix

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 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
LCK p.Asn40Ser Uncertain significance ★★ ⚠ same condition
LCK p.Asp187Gly 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-asp283 (accessed [today's date]).

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