Is CARD18 p.Val50Asp (c.149T>A) pathogenic?

CARD18 p.Val50Asp (c.149T>A) is classified Uncertain significance in CARD18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.2068); Ultra-rare (popmax 0.045%, amr).

How common is CARD18 p.Val50Asp (c.149T>A) in the general population?

CARD18 p.Val50Asp (c.149T>A) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about CARD18 p.Val50Asp (c.149T>A)?

AlphaMissense predicts likely benign (score 0.2068) — an in-silico prediction, not a clinical call.

CARD18 p.Val50Asp

c.149T>A · VCV3484973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2068	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9
Regional constraint	o/e 1.27	unconstrained · MANE · 910 bp · p 0.0055 · regional, not allelic
Overall
CADD	4.709	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.045% Admixed American · 27/59,972 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00167% 27/1,613,666 alleles · ultra-rare

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: CARD18
Protein: p.Val50Asp
Coding: c.149T>A
MANE Select: NM_021571
Type: single nucleotide variant
Location: chr11:105138937 (GRCh38)
Gene constraint: LOEUF 1.545 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.56 · 1 PDB
Residue 50: the card domain; an α-helix

Full CARD18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CARD18 p.Ala19Ser Uncertain significance ★ ⚠ same type
CARD18 p.Ala2Val Uncertain significance ★ ⚠ same type
CARD18 p.Ala54Ser Uncertain significance ★ ⚠ same type
CARD18 p.Arg10Gly Uncertain significance ★ ⚠ same type
CARD18 p.Ile35Thr Uncertain significance ★ ⚠ same type
CARD18 p.Leu26Pro Uncertain significance ★ ⚠ same type
CARD18 p.Leu30Ile Uncertain significance ★ ⚠ same type
CARD18 p.Leu60Phe 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/card18-p-val50asp (accessed [today's date]).

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