Is STK4 p.Asp359= (c.1077C>T) pathogenic?

STK4 p.Asp359= (c.1077C>T) is classified Likely benign in STK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). Ultra-rare (popmax 0.0512%, eas); Associated with combined immunodeficiency due to STK4 deficiency.

What condition is associated with STK4 p.Asp359= (c.1077C>T)?

STK4 p.Asp359= (c.1077C>T) is associated with combined immunodeficiency due to STK4 deficiency (ClinVar).

How common is STK4 p.Asp359= (c.1077C>T) in the general population?

STK4 p.Asp359= (c.1077C>T) is ultra-rare (popmax 0.0512%, eas) (gnomAD).

STK4 p.Asp359=

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.1077C>T · rs561228188 · VCV1096703

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, eas)

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 0.8	GERP 0.021, phastCons 1
Overall
CADD	8.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% East Asian · 23/44,884 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00161% 26/1,614,146 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0512%	1,951
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	8.47e-05%	1,180,011

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.Asp359=
Coding: c.1077C>T
MANE Select: NM_006282
dbSNP: rs561228188
Type: single nucleotide variant
Location: chr20:45001283 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 16 PDB

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.Asp359Glu Uncertain significance ★ ⚠ same residue
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

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-asp359 (accessed [today's date]).

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