Is CARD6 p.Ser712Arg (c.2134A>C) pathogenic?

CARD6 p.Ser712Arg (c.2134A>C) is classified Uncertain significance in CARD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely benign (0.2101); Absent from gnomAD v4.1.

How common is CARD6 p.Ser712Arg (c.2134A>C) in the general population?

CARD6 p.Ser712Arg (c.2134A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CARD6 p.Ser712Arg (c.2134A>C)?

AlphaMissense predicts likely benign (score 0.2101) — an in-silico prediction, not a clinical call.

CARD6 p.Ser712Arg

c.2134A>C · rs2478010178 · VCV2619165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2101 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2101	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -6.43	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 2.6	GERP -0.29, phastCons 0.004
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.91 · regional, not allelic
Overall
CADD	6.298	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

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: CARD6
Protein: p.Ser712Arg
Coding: c.2134A>C
MANE Select: NM_032587
dbSNP: rs2478010178
Type: single nucleotide variant
Location: chr5:40853466 (GRCh38)
Gene constraint: LOEUF 1.487 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.25

Full CARD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CARD6 p.Arg93Lys Benign ★★ same type
CARD6 p.Cys185Tyr Benign ★★ same type
CARD6 p.Gly264Glu Benign ★★ same type
CARD6 p.Ile194Val Benign ★★ same type
CARD6 p.Ala1022Asp Uncertain significance ★ ⚠ same type
CARD6 p.Ala110Thr Conflicting classifications of pathogenicity ★ ⚠ same type
CARD6 p.Ala159Thr Uncertain significance ★ ⚠ same type
CARD6 p.Ala340Thr 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/card6-p-ser712arg (accessed [today's date]).

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