Is LCK p.Ser162= (c.486G>A) pathogenic?

LCK p.Ser162= (c.486G>A) is classified Likely benign in LCK (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-14). Very rare (popmax 0.00267%, afr); Associated with severe combined immunodeficiency due to LCK deficiency.

What condition is associated with LCK p.Ser162= (c.486G>A)?

LCK p.Ser162= (c.486G>A) is associated with severe combined immunodeficiency due to LCK deficiency (ClinVar).

How common is LCK p.Ser162= (c.486G>A) in the general population?

LCK p.Ser162= (c.486G>A) is very rare (popmax 0.00267%, afr) (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.Ser162=

c.486G>A · rs1126767 · VCV2712338

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -4.8
Overall
CADD	9.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,924 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,462
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000339%	294,999

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.Ser162=
Coding: c.486G>A
MANE Select: NM_005356
dbSNP: rs1126767
Type: single nucleotide variant
Location: chr1:32275918 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 57 PDB
Residue 162: a modified residue (phosphoserine); the sh2 domain; the 'interaction with ptprh' 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 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-ser162 (accessed [today's date]).

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