Is STING1 p.Pro11= (c.33G>C) pathogenic?

STING1 p.Pro11= (c.33G>C) is classified Likely benign in STING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). Very rare (popmax 0.00134%, afr); Associated with STING-associated vasculopathy with onset in infancy.

What condition is associated with STING1 p.Pro11= (c.33G>C)?

STING1 p.Pro11= (c.33G>C) is associated with STING-associated vasculopathy with onset in infancy (ClinVar).

How common is STING1 p.Pro11= (c.33G>C) in the general population?

STING1 p.Pro11= (c.33G>C) is very rare (popmax 0.00134%, afr) (gnomAD).

STING1 p.Pro11=

Q: How is STING-associated vasculopathy with onset in infancy inherited?

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

c.33G>C · VCV4707249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

STING-associated vasculopathy with onset in infancy

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 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4	GERP -3.5
Overall
CADD	0.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,790 alleles

Overall 0.000124% 2/1,609,526 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,232
African / African-Americangrpmax	0.00134%	74,790

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: STING1
Protein: p.Pro11=
Coding: c.33G>C
MANE Select: NM_198282
Type: single nucleotide variant
Location: chr5:139481672 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.13 · 125 PDB
Residue 11: the 'mediates interaction with zdhhc1 and zdhhc11' region; an α-helix

Full STING1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

STING-associated vasculopathy with onset in infancy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For STING-associated vasculopathy with onset in infancy (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

STING1 p.Pro11Leu Uncertain significance ★★ same residue
STING1 p.Arg281Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
STING1 p.Arg284Ser Pathogenic ★★ same condition
STING1 p.Val155Met Pathogenic ★★ ⚠ same condition
STING1 c.946+1G>T Uncertain significance ★★ same condition
STING1 p.Ala22Asp Uncertain significance ★★ ⚠ same condition
STING1 p.Ala233Thr Uncertain significance ★★ same condition
STING1 p.Ala254Val 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/sting1-p-pro11 (accessed [today's date]).

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