Is STK4 p.Pro390= (c.1170T>C) pathogenic?

STK4 p.Pro390= (c.1170T>C) is classified Likely benign in STK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). Ultra-rare (popmax 0.0165%, mid); Associated with combined immunodeficiency due to STK4 deficiency.

What condition is associated with STK4 p.Pro390= (c.1170T>C)?

STK4 p.Pro390= (c.1170T>C) is associated with combined immunodeficiency due to STK4 deficiency (ClinVar).

How common is STK4 p.Pro390= (c.1170T>C) in the general population?

STK4 p.Pro390= (c.1170T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

STK4 p.Pro390=

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.1170T>C · rs2068319036 · VCV2187574

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 0.24	GERP 0.81, phastCons 1
Overall
CADD	8.749	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,052 alleles

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

Overall 0.00031% 5/1,611,828 alleles · ultra-rare exomes 5/1,459,454 · genomes 0/152,374 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,052
African / African-American	0.00267%	37,488
Remaining individualsnot grpmax-eligible	0.0016%	62,406
South Asian	0.0011%	90,710

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.Pro390=
Coding: c.1170T>C
MANE Select: NM_006282
dbSNP: rs2068319036
Type: single nucleotide variant
Location: chr20:45024995 (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.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-pro390 (accessed [today's date]).

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