Is C2CD3 p.Arg1851Cys (c.5551C>T) pathogenic?

C2CD3 p.Arg1851Cys (c.5551C>T) is classified Uncertain significance in C2CD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-17). AlphaMissense: likely benign (0.2337); Very rare (popmax 0.00271%, afr).

How common is C2CD3 p.Arg1851Cys (c.5551C>T) in the general population?

C2CD3 p.Arg1851Cys (c.5551C>T) is very rare (popmax 0.00271%, afr) (gnomAD).

What do computational predictors say about C2CD3 p.Arg1851Cys (c.5551C>T)?

AlphaMissense predicts likely benign (score 0.2337) — an in-silico prediction, not a clinical call.

C2CD3 p.Arg1851Cys

c.5551C>T · rs1232565234 · VCV1981495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2337 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2337	likely benign
REVEL	0.765	pathogenic-leaning
SaProt	LLR -7.60	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	33.0	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 0.00271% African / African-American · 2/73,838 alleles

Filtering AF 0.00045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000683% 11/1,611,464 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00271%	36,919
European (non-Finnish)	0.000763%	131,082

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.Arg1851Cys
Coding: c.5551C>T
MANE Select: NM_001286577
dbSNP: rs1232565234
Type: single nucleotide variant
Location: chr11:74042163 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65

Full C2CD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD3 p.Arg1851His Uncertain significance ★★ ⚠ same residue
C2CD3 c.3911-2A>T Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg621Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg666Ter Pathogenic ★★ same type
C2CD3 p.Arg768Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Tyr173Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 c.2085+5G>A Uncertain significance ★★ same type
C2CD3 c.4951+6C>T 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/c2cd3-p-arg1851cys (accessed [today's date]).

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