Is CARD14 p.Lys897fs (c.2690del) pathogenic?

CARD14 p.Lys897fs (c.2690del) is classified Uncertain significance in CARD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). Very rare (popmax 0.00216%, amr); Associated with pityriasis rubra pilaris.

What condition is associated with CARD14 p.Lys897fs (c.2690del)?

CARD14 p.Lys897fs (c.2690del) is associated with pityriasis rubra pilaris, psoriasis 2 (ClinVar).

How common is CARD14 p.Lys897fs (c.2690del) in the general population?

CARD14 p.Lys897fs (c.2690del) is very rare (popmax 0.00216%, amr) (gnomAD).

CARD14 p.Lys897fs

c.2690del · rs2510780528 · VCV1943516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00216%, amr)

Conditions

pityriasis rubra pilaris

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 22 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP -1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00216% Admixed American · 1/46,302 alleles

Overall 8.31e-05% 1/1,202,726 alleles · very rare exomes 1/1,055,456 · genomes 0/147,270 · 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: CARD14
Protein: p.Lys897fs
Coding: c.2690del
MANE Select: NM_001366385
dbSNP: rs2510780528
Type: Deletion
Location: chr17:80205648 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.89
Residue 897: the guanylate kinase-like domain

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

Disease context

pityriasis rubra pilaris — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: psoriasis 2

Similar variants

CARD14 p.Trp497fs Uncertain significance ★★ same condition
CARD14 c.1356+18_1356+19del Benign/Likely benign ★★ same condition
CARD14 c.1499+27_1499+55del Likely benign ★★ same condition
CARD14 c.1356+8del Conflicting classifications of pathogenicity ★ same condition
CARD14 c.1357-8_1357-3del Uncertain significance ★ same condition
CARD14 c.1593_1594+1del Uncertain significance ★ same condition
CARD14 c.1793_1851+33del Uncertain significance ★ same condition
CARD14 p.Ala131fs 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-lys897fs (accessed [today's date]).

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