Is C2CD3 p.Arg1195Gln (c.3584G>A) pathogenic?

C2CD3 p.Arg1195Gln (c.3584G>A) is classified Uncertain significance in C2CD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: likely benign (0.085); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with C2CD3 p.Arg1195Gln (c.3584G>A)?

C2CD3 p.Arg1195Gln (c.3584G>A) is associated with Inborn genetic diseases (ClinVar).

How common is C2CD3 p.Arg1195Gln (c.3584G>A) in the general population?

C2CD3 p.Arg1195Gln (c.3584G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about C2CD3 p.Arg1195Gln (c.3584G>A)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

C2CD3 p.Arg1195Gln

c.3584G>A · rs758046987 · VCV3135869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.07	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 0.12	GERP 1.7, phastCons 0.91
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	16.01	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 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000558% 9/1,613,928 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
South Asian	0.0022%	45,543
Admixed American	0.00167%	60,000
Finnishnot grpmax-eligible	0.00156%	64,038
European (non-Finnish)	0.000339%	294,996

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: C2CD3
Protein: p.Arg1195Gln
Coding: c.3584G>A
MANE Select: NM_001286577
dbSNP: rs758046987
Type: single nucleotide variant
Location: chr11:74090870 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 1195: the c2 4 domain

Full C2CD3 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

C2CD3 c.2085+5G>A Uncertain significance ★★ same condition
C2CD3 c.4951+6C>T Uncertain significance ★★ same condition
C2CD3 p.Ala1382Pro Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala1777Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala95Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1122Ile Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1145His Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1183His 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/c2cd3-p-arg1195gln (accessed [today's date]).

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