Is CARD14 p.Ser307= (c.921G>A) pathogenic?

CARD14 p.Ser307= (c.921G>A) is classified Conflicting classifications of pathogenicity in CARD14 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-17). Very rare (popmax 0.00414%, afr); Associated with autoinflammatory syndrome.

What condition is associated with CARD14 p.Ser307= (c.921G>A)?

CARD14 p.Ser307= (c.921G>A) is associated with autoinflammatory syndrome, psoriasis 2, pityriasis rubra pilaris (ClinVar).

How common is CARD14 p.Ser307= (c.921G>A) in the general population?

CARD14 p.Ser307= (c.921G>A) is very rare (popmax 0.00414%, afr) (gnomAD).

CARD14 p.Ser307=

c.921G>A · rs753922155 · VCV1159232

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00414%, afr)

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 -13	GERP -3.5
Overall
CADD	0.097	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00414% African / African-American · 3/72,416 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00189% 30/1,586,550 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00414%	24,139
East Asian	0.00234%	42,754
South Asian	0.00228%	43,890
Admixed American	0.00189%	52,932
European (non-Finnish)	0.00188%	53,223
Remaining individualsnot grpmax-eligible	0.00163%	61,270

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.Ser307=
Coding: c.921G>A
MANE Select: NM_001366385
dbSNP: rs753922155
Type: single nucleotide variant
Location: chr17:80189830 (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.Ser307Leu 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-ser307 (accessed [today's date]).

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