Is STK4 p.Ser40= (c.120C>G) pathogenic?

STK4 p.Ser40= (c.120C>G) is classified Likely benign in STK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). Very rare (popmax 0.0011%, sas); Associated with combined immunodeficiency due to STK4 deficiency.

What condition is associated with STK4 p.Ser40= (c.120C>G)?

STK4 p.Ser40= (c.120C>G) is associated with combined immunodeficiency due to STK4 deficiency (ClinVar).

How common is STK4 p.Ser40= (c.120C>G) in the general population?

STK4 p.Ser40= (c.120C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

STK4 p.Ser40=

Q: How is Combined immunodeficiency due to STK4 deficiency inherited?

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

c.120C>G · rs750961060 · VCV1663656

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

combined immunodeficiency due to STK4 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 1.1	GERP -4.1, phastCons 1
Overall
CADD	5.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,886 alleles

Overall 6.2e-05% 1/1,613,096 alleles · very rare exomes 1/1,460,826 · genomes 0/152,270 · joint denominator

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: STK4
Protein: p.Ser40=
Coding: c.120C>G
MANE Select: NM_006282
dbSNP: rs750961060
Type: single nucleotide variant
Location: chr20:44978446 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 16 PDB
Residue 40: a binding site; the protein kinase domain

Full STK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to STK4 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to STK4 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

STK4 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same condition
STK4 p.Arg117Ter Pathogenic ★★ same condition
STK4 p.Arg148Ter Pathogenic ★★ same condition
STK4 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
STK4 p.Ala391Val Uncertain significance ★★ ⚠ same condition
STK4 p.Ala479Ser Uncertain significance ★★ ⚠ same condition
STK4 p.Arg310Gln Uncertain significance ★★ ⚠ same condition
STK4 p.Arg310Pro 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/stk4-p-ser40 (accessed [today's date]).

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