Is CARD14 p.Ser116= (c.348C>T) pathogenic?

CARD14 p.Ser116= (c.348C>T) is classified Uncertain significance in CARD14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-27). Ultra-rare (popmax 0.0164%, mid); Associated with pityriasis rubra pilaris.

What condition is associated with CARD14 p.Ser116= (c.348C>T)?

CARD14 p.Ser116= (c.348C>T) is associated with pityriasis rubra pilaris, psoriasis 2, autoinflammatory syndrome (ClinVar).

How common is CARD14 p.Ser116= (c.348C>T) in the general population?

CARD14 p.Ser116= (c.348C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CARD14 p.Ser116=

c.348C>T · rs775819149 · VCV659668

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

pityriasis rubra pilaris

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 -7.4	GERP -2.2
Overall
CADD	0.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000743% 12/1,613,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
South Asian	0.0022%	45,544
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	64,034
African / African-American	0.00133%	74,922
European (non-Finnish)	0.000508%	196,663

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.Ser116=
Coding: c.348C>T
MANE Select: NM_001366385
dbSNP: rs775819149
Type: single nucleotide variant
Location: chr17:80182789 (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

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

Also linked: psoriasis 2 autoinflammatory syndrome

Similar variants

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
CARD14 p.Ala208Val 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-ser116 (accessed [today's date]).

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