Is CARD10 p.Val449= (c.1347T>G) pathogenic?

CARD10 p.Val449= (c.1347T>G) is classified Benign in CARD10 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-09-18). Common (popmax 21.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CARD10-related disorder.

What condition is associated with CARD10 p.Val449= (c.1347T>G)?

CARD10 p.Val449= (c.1347T>G) is associated with CARD10-related disorder (ClinVar).

CARD10 p.Val449=

Q: How common is CARD10 p.Val449= (c.1347T>G) in the general population?

CARD10 p.Val449= (c.1347T>G) is common (popmax 21.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1347T>G · rs61742320 · VCV3057027

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 21.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CARD10-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.5	GERP -2.8
Overall
CADD	0.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.2% African / African-American · 15,799/74,370 alleles

Filtering AF 21% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.9%

Overall 1.43% 22,784/1,595,330 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.2%	5
Middle Eastern	2.45%	41
Remaining individualsnot grpmax-eligible	1.82%	55
Admixed American	1.7%	59
Ashkenazi Jewishnot grpmax-eligible	0.604%	166
South Asian	0.381%	262
European (non-Finnish)	0.346%	289
Finnishnot grpmax-eligible	0.273%	366

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: CARD10
Protein: p.Val449=
Coding: c.1347T>G
MANE Select: NM_014550
dbSNP: rs61742320
Type: single nucleotide variant
Location: chr22:37506228 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.22

Full CARD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CARD10-related disorder

Similar variants

CARD10 p.Val449Phe Uncertain significance ★ ⚠ same residue
CARD10 p.Ala1032Asp Uncertain significance ⚠ same condition
CARD10 p.Glu1019Gln Uncertain significance ⚠ same condition
CARD10 c.1383+7G>A Likely benign same condition
CARD10 c.2477-7G>C Likely benign same condition
CARD10 c.910-6C>T Benign same condition
CARD10 p.Ala528= Benign same condition
CARD10 p.Ala7= 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/card10-p-val449 (accessed [today's date]).

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