Is CARD8 p.Ser403Ala (c.1207T>G) pathogenic?

CARD8 p.Ser403Ala (c.1207T>G) is classified Uncertain significance in CARD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). Absent from gnomAD v4.1; Associated with inflammatory bowel disease 30.

What condition is associated with CARD8 p.Ser403Ala (c.1207T>G)?

CARD8 p.Ser403Ala (c.1207T>G) is associated with inflammatory bowel disease 30 (ClinVar).

How common is CARD8 p.Ser403Ala (c.1207T>G) in the general population?

CARD8 p.Ser403Ala (c.1207T>G) is absent from gnomAD v4.1 (gnomAD).

CARD8 p.Ser403Ala

c.1207T>G · VCV3393338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

inflammatory bowel disease 30

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.072	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -1.3, phastCons 0.79
Regional constraint	o/e 0.86	unconstrained · MANE · 29 kb · p 0.00022 · regional, not allelic
Overall
CADD	14.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CARD8
Protein: p.Ser403Ala
Coding: c.1207T>G
MANE Select: NM_001184900
Type: single nucleotide variant
Location: chr19:48218967 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.42 · 5 PDB
Residue 403: a UniProt-annotated variant site (in ibd30); the fiind domain; the 'upa' region

Full CARD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inflammatory bowel disease 30 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CARD8 p.Ser403Thr Uncertain significance ★ same residue
CARD8 p.Glu285Ter Uncertain significance ★★ same condition
CARD8 p.His324Tyr Uncertain significance ★★ same condition
CARD8 p.Ser181Asn Uncertain significance ★★ same condition
CARD8 p.Asp92Gly Uncertain significance ★ same condition
CARD8 p.Ser47Gly Uncertain significance ★ same condition
CARD8 p.Val44Ile Uncertain significance ★ same condition
CARD8 p.Phe211Cys Likely benign ★ 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/card8-p-ser403ala (accessed [today's date]).

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