Is CARD8 p.Asp511fs (c.1527_1528del) pathogenic?

CARD8 p.Asp511fs (c.15271528del) is classified Uncertain significance in CARD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-29). Very rare (popmax 0.00223%, eas).

How common is CARD8 p.Asp511fs (c.1527_1528del) in the general population?

CARD8 p.Asp511fs (c.1527_1528del) is very rare (popmax 0.00223%, eas) (gnomAD).

CARD8 p.Asp511fs

c.1527_1528del · VCV4797935

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 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.99	GERP 0.91, phastCons 0.23

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000205% 3/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
South Asian	0.0022%	45,539

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: CARD8
Protein: p.Asp511fs
Coding: c.1527_1528del
MANE Select: NM_001184900
Type: Deletion
Location: chr19:48211796 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.42 · 5 PDB
Residue 511: the card domain; an α-helix

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

Similar variants

CARD8 p.Ala244fs Uncertain significance ★ same type
CARD8 p.Asp92fs Uncertain significance ★ same type
CARD8 p.Glu14fs Uncertain significance ★ same type
CARD8 p.His249fs Uncertain significance ★ same type
CARD8 p.Leu334fs Uncertain significance ★ same type
CARD8 p.Leu382_Lys383insTer Uncertain significance ★ same type
CARD8 p.Ser373fs Uncertain significance ★ same type
CARD8 p.Thr494_Lys498del Uncertain significance ★ same type

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-asp511fs (accessed [today's date]).

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