Is CARD14 p.Ile30= (c.90C>T) pathogenic?

CARD14 p.Ile30= (c.90C>T) is classified Conflicting classifications of pathogenicity in CARD14 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-18). Very rare (popmax 0.00805%, sas); Associated with autoinflammatory syndrome.

What condition is associated with CARD14 p.Ile30= (c.90C>T)?

CARD14 p.Ile30= (c.90C>T) is associated with autoinflammatory syndrome, psoriasis 2, pityriasis rubra pilaris (ClinVar).

How common is CARD14 p.Ile30= (c.90C>T) in the general population?

CARD14 p.Ile30= (c.90C>T) is very rare (popmax 0.00805%, sas) (gnomAD).

CARD14 p.Ile30=

c.90C>T · rs549347508 · VCV1592658

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00805%, sas)

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.1	GERP -3.2
Overall
CADD	1.584	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00805% South Asian · 7/86,904 alleles

Filtering AF 0.00374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00265%

Overall 0.000945% 15/1,587,238 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00805%	12,415
Remaining individualsnot grpmax-eligible	0.00488%	20,490
East Asian	0.00231%	43,220
European (non-Finnish)	0.000343%	291,799

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: CARD14
Protein: p.Ile30=
Coding: c.90C>T
MANE Select: NM_001366385
dbSNP: rs549347508
Type: single nucleotide variant
Location: chr17:80181528 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.89
Residue 30: the card domain

Full CARD14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: psoriasis 2 pityriasis rubra pilaris

Similar variants

CARD14 p.Ile30fs Uncertain significance ★ same residue
CARD14 c.349+1G>A Pathogenic ★★ same condition
CARD14 p.Leu156Pro Pathogenic/Likely pathogenic ★★ same condition
CARD14 p.Met119Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CARD14 c.1089+5C>G Uncertain significance ★★ same condition
CARD14 c.1357-1G>A Uncertain significance ★★ same condition
CARD14 c.2569+2T>A Uncertain significance ★★ same condition
CARD14 c.963+5C>T 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/card14-p-ile30 (accessed [today's date]).

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