Is CGAS p.Ala30Ser (c.88G>T) pathogenic?

CGAS p.Ala30Ser (c.88G>T) is classified Uncertain significance in CGAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0861); Absent from gnomAD v4.1.

How common is CGAS p.Ala30Ser (c.88G>T) in the general population?

CGAS p.Ala30Ser (c.88G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CGAS p.Ala30Ser (c.88G>T)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

CGAS p.Ala30Ser

c.88G>T · VCV4227464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,584,418)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.94	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 -1.5	GERP -2.3
Regional constraint	o/e 1.02	unconstrained · MANE · 6,445 bp · p 0.71 · regional, not allelic
Overall
CADD	3.274	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

No allele count reported in gnomAD v4.1 (AN 1,584,418). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CGAS
Protein: p.Ala30Ser
Coding: c.88G>T
MANE Select: NM_138441
Type: single nucleotide variant
Location: chr6:73452094 (GRCh38)
Gene constraint: LOEUF 1.529 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 107 PDB
Residue 30: the 'dna-binding' region; the 'disordered' region

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

Similar variants

CGAS p.Ala109Glu Uncertain significance ★ ⚠ same type
CGAS p.Ala118Asp Uncertain significance ★ ⚠ same type
CGAS p.Ala158Val Uncertain significance ★ ⚠ same type
CGAS p.Ala167Pro Uncertain significance ★ ⚠ same type
CGAS p.Ala167Val Uncertain significance ★ ⚠ same type
CGAS p.Ala17Gly Conflicting classifications of pathogenicity ★ ⚠ same type
CGAS p.Ala247Glu Uncertain significance ★ ⚠ same type
CGAS p.Ala24Ser Uncertain significance ★ ⚠ same type

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/cgas-p-ala30ser (accessed [today's date]).

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