Is CARD14 p.Pro625fs (c.1874_1886del) pathogenic?

CARD14 p.Pro625fs (c.18741886del) is classified Uncertain significance in CARD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). Very rare (popmax 0.000169%, nfe); Associated with pityriasis rubra pilaris.

What condition is associated with CARD14 p.Pro625fs (c.1874_1886del)?

CARD14 p.Pro625fs (c.1874_1886del) is associated with pityriasis rubra pilaris, psoriasis 2 (ClinVar).

How common is CARD14 p.Pro625fs (c.1874_1886del) in the general population?

CARD14 p.Pro625fs (c.1874_1886del) is very rare (popmax 0.000169%, nfe) (gnomAD).

CARD14 p.Pro625fs

c.1874_1886del · VCV4792567

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 0.000169%, nfe)

Conditions

pityriasis rubra pilaris

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3	GERP -2.9, phastCons 0.98

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,964 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,020 alleles · very rare exomes 2/1,461,758 · genomes 0/152,262 · 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.Pro625fs
Coding: c.1874_1886del
MANE Select: NM_001366385
Type: Deletion
Location: chr17:80201764 (GRCh38)

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

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-pro625fs (accessed [today's date]).

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