Is CGAS p.Asp90Val (c.269A>T) pathogenic?

CGAS p.Asp90Val (c.269A>T) is classified Uncertain significance in CGAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.1); Absent from gnomAD v4.1.

How common is CGAS p.Asp90Val (c.269A>T) in the general population?

CGAS p.Asp90Val (c.269A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CGAS p.Asp90Val (c.269A>T)?

AlphaMissense predicts likely benign (score 0.1) — an in-silico prediction, not a clinical call.

CGAS p.Asp90Val

c.269A>T · VCV4001908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.83	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 -1.3	GERP -3.4
Regional constraint	o/e 1.02	unconstrained · MANE · 6,445 bp · p 0.71 · regional, not allelic
Overall
CADD	18.05	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CGAS
Protein: p.Asp90Val
Coding: c.269A>T
MANE Select: NM_138441
Type: single nucleotide variant
Location: chr6:73451913 (GRCh38)
Gene constraint: LOEUF 1.529 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 107 PDB
Residue 90: 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-asp90val (accessed [today's date]).

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