Is IFIH1 p.Lys894= (c.2682G>A) pathogenic?

IFIH1 p.Lys894= (c.2682G>A) is classified Benign/Likely benign in IFIH1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0388%, nfe); Associated with Aicardi-Goutieres syndrome 7.

What condition is associated with IFIH1 p.Lys894= (c.2682G>A)?

IFIH1 p.Lys894= (c.2682G>A) is associated with Aicardi-Goutieres syndrome 7, Singleton-Merten syndrome 1 (ClinVar).

How common is IFIH1 p.Lys894= (c.2682G>A) in the general population?

IFIH1 p.Lys894= (c.2682G>A) is ultra-rare (popmax 0.0388%, nfe) (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.Lys894=

c.2682G>A · rs374488772 · VCV703947

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0388%, nfe)

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 0.2	GERP -0.11, phastCons 0.86
Overall
CADD	5.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0388% European (non-Finnish) · 457/1,178,900 alleles

Filtering AF 0.0358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0346%

Overall 0.0293% 472/1,612,570 alleles · ultra-rare exomes 447/1,460,398 · genomes 25/152,172 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0388%	2,580
Remaining individualsnot grpmax-eligible	0.0112%	8,917
African / African-American	0.00801%	12,479
Admixed American	0.00167%	59,948
Finnishnot grpmax-eligible	0.00156%	63,994

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.Lys894=
Coding: c.2682G>A
MANE Select: NM_022168
dbSNP: rs374488772
Type: single nucleotide variant
Location: chr2:162268212 (GRCh38)
Gene constraint: LOEUF 1.406 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 13 PDB
Residue 894: a UniProt-annotated variant site (in imd95; no protein detected by western blot in homozygous patient cells); the rlr ctr 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-lys894 (accessed [today's date]).

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