Is STING1 p.Pro2Ser (c.4C>T) pathogenic?

STING1 p.Pro2Ser (c.4C>T) is classified Uncertain significance in STING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). AlphaMissense: likely benign (0.0856); Very rare (popmax 0.00437%, nfe); Associated with STING-associated vasculopathy with onset in infancy.

What condition is associated with STING1 p.Pro2Ser (c.4C>T)?

STING1 p.Pro2Ser (c.4C>T) is associated with STING-associated vasculopathy with onset in infancy (ClinVar).

How common is STING1 p.Pro2Ser (c.4C>T) in the general population?

STING1 p.Pro2Ser (c.4C>T) is very rare (popmax 0.00437%, nfe) (gnomAD).

What do computational predictors say about STING1 p.Pro2Ser (c.4C>T)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

STING1 p.Pro2Ser

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.4C>T · rs1223377482 · VCV948262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00437%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

STING-associated vasculopathy with onset in infancy

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -3.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 5,440 bp · p 3e-07 · regional, not allelic
Overall
CADD	9.879	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00437% European (non-Finnish) · 51/1,166,556 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00305%

Overall 0.0032% 51/1,596,158 alleles · very rare

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.Pro2Ser
Coding: c.4C>T
MANE Select: NM_198282
dbSNP: rs1223377482
Type: single nucleotide variant
Location: chr5:139481701 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.13 · 125 PDB
Residue 2: the 'mediates interaction with zdhhc1 and zdhhc11' region

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.Pro2Leu 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-pro2ser (accessed [today's date]).

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