Is CARD14 p.Arg29Ser (c.87G>C) pathogenic?

CARD14 p.Arg29Ser (c.87G>C) is classified Uncertain significance in CARD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: ambiguous (0.362); Very rare (popmax 6.96e-05%); Associated with Inborn genetic diseases.

What condition is associated with CARD14 p.Arg29Ser (c.87G>C)?

CARD14 p.Arg29Ser (c.87G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CARD14 p.Arg29Ser (c.87G>C) in the general population?

CARD14 p.Arg29Ser (c.87G>C) is very rare (popmax 6.96e-05%) (gnomAD).

What do computational predictors say about CARD14 p.Arg29Ser (c.87G>C)?

AlphaMissense predicts ambiguous (score 0.362) — an in-silico prediction, not a clinical call.

CARD14 p.Arg29Ser

c.87G>C · rs2510554405 · VCV2294775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.96e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.362	ambiguous
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.43, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.27 · regional, not allelic
Overall
CADD	15.35	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.96e-05%

Overall 6.96e-05% 1/1,436,206 alleles · very 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: CARD14
Protein: p.Arg29Ser
Coding: c.87G>C
MANE Select: NM_001366385
dbSNP: rs2510554405
Type: single nucleotide variant
Location: chr17:80181525 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.89
Residue 29: the card domain

Full CARD14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CARD14 p.Arg29Lys Uncertain significance ★ ⚠ same residue
CARD14 p.Ala208Val Uncertain significance ★★ ⚠ same condition
CARD14 p.Ala254Thr Uncertain significance ★★ ⚠ same condition
CARD14 p.Ala349Val Uncertain significance ★★ ⚠ same condition
CARD14 p.Ala367Val Uncertain significance ★★ ⚠ same condition
CARD14 p.Ala477Thr Uncertain significance ★★ ⚠ same condition
CARD14 p.Ala573Val Uncertain significance ★★ ⚠ same condition
CARD14 p.Ala731Thr 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-arg29ser (accessed [today's date]).

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