Is IFIH1 p.Pro482= (c.1446T>C) pathogenic?

IFIH1 p.Pro482= (c.1446T>C) is classified Likely benign in IFIH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Very rare (popmax 0.00167%, amr); Associated with Aicardi-Goutieres syndrome 7.

What condition is associated with IFIH1 p.Pro482= (c.1446T>C)?

IFIH1 p.Pro482= (c.1446T>C) is associated with Aicardi-Goutieres syndrome 7, Singleton-Merten syndrome 1 (ClinVar).

How common is IFIH1 p.Pro482= (c.1446T>C) in the general population?

IFIH1 p.Pro482= (c.1446T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Aicardi-Goutières syndrome inherited?

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

IFIH1 p.Pro482=

c.1446T>C · rs1411002338 · VCV1119712

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Aicardi-Goutieres syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -0.57, phastCons 0.99
Overall
CADD	6.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,824 alleles

Overall 6.2e-05% 1/1,612,694 alleles · very rare exomes 1/1,460,726 · genomes 0/151,968 · joint denominator

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: IFIH1
Protein: p.Pro482=
Coding: c.1446T>C
MANE Select: NM_022168
dbSNP: rs1411002338
Type: single nucleotide variant
Location: chr2:162281406 (GRCh38)
Gene constraint: LOEUF 1.406 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 13 PDB
Residue 482: the helicase atp-binding domain

Full IFIH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Aicardi-Goutieres syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Singleton-Merten syndrome 1

For Aicardi-Goutières syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

IFIH1 p.Arg720Gln Pathogenic ★★ ⚠ same condition
IFIH1 p.Arg779Cys Pathogenic ★★ ⚠ same condition
IFIH1 p.Arg779His Pathogenic/Likely pathogenic ★★ ⚠ same condition
IFIH1 p.Arg779Leu Pathogenic/Likely pathogenic ★★ same condition
IFIH1 p.Arg822Gln Pathogenic/Likely pathogenic ★★ same condition
IFIH1 p.Gly495Arg Likely pathogenic ★★ ⚠ same condition
IFIH1 c.1525-1G>A Uncertain significance ★★ same condition
IFIH1 c.1641+2T>C 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/ifih1-p-pro482 (accessed [today's date]).

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