Is CARD14 p.Cys355= (c.1065C>T) pathogenic?

CARD14 p.Cys355= (c.1065C>T) is classified Benign/Likely benign in CARD14 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-24). Rare (popmax 0.728%, afr); Associated with autoinflammatory syndrome.

What condition is associated with CARD14 p.Cys355= (c.1065C>T)?

CARD14 p.Cys355= (c.1065C>T) is associated with autoinflammatory syndrome, psoriasis 2, pityriasis rubra pilaris (ClinVar).

How common is CARD14 p.Cys355= (c.1065C>T) in the general population?

CARD14 p.Cys355= (c.1065C>T) is rare (popmax 0.728%, afr) (gnomAD).

CARD14 p.Cys355=

c.1065C>T · rs140246774 · VCV458083

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.728%, afr)

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.35	donor gain · deltas
Constraint at this position
Conservation	phyloP -20	GERP -2.2
Overall
CADD	9.571	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.728% African / African-American · 546/75,000 alleles

Filtering AF 0.677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.657%

Overall 0.0402% 649/1,613,852 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.728%	137
Admixed American	0.085%	1,177
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.00203%	49,167
South Asian	0.0011%	91,076

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.Cys355=
Coding: c.1065C>T
MANE Select: NM_001366385
dbSNP: rs140246774
Type: single nucleotide variant
Location: chr17:80190875 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.89

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.Cys355Tyr 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-cys355 (accessed [today's date]).

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