Is C2CD2 p.Ser184Gly (c.550A>G) pathogenic?

C2CD2 p.Ser184Gly (c.550A>G) is classified Uncertain significance in C2CD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.075); Very rare (popmax 0.0011%, sas).

How common is C2CD2 p.Ser184Gly (c.550A>G) in the general population?

C2CD2 p.Ser184Gly (c.550A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about C2CD2 p.Ser184Gly (c.550A>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

C2CD2 p.Ser184Gly

c.550A>G · rs2516952235 · VCV2308606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.22	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 -0.015	GERP -3.7, phastCons 0.002
Regional constraint	o/e 0.87	unconstrained · MANE · 65 kb · p 0.00014 · regional, not allelic
Overall
CADD	13.2	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 0.0011% South Asian · 1/91,084 alleles

Overall 6.84e-05% 1/1,461,866 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: C2CD2
Protein: p.Ser184Gly
Coding: c.550A>G
MANE Select: NM_015500
dbSNP: rs2516952235
Type: single nucleotide variant
Location: chr21:41918903 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.52
Residue 184: the smp-lbd domain

Full C2CD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD2 p.Pro104= Benign ★★ same type
C2CD2 p.Ala123Val Uncertain significance ★ ⚠ same type
C2CD2 p.Ala136Gly Uncertain significance ★ ⚠ same type
C2CD2 p.Ala146Val Uncertain significance ★ ⚠ same type
C2CD2 p.Ala189Thr Uncertain significance ★ ⚠ same type
C2CD2 p.Ala207Val Uncertain significance ★ ⚠ same type
C2CD2 p.Ala345Val Uncertain significance ★ ⚠ same type
C2CD2 p.Ala466Thr 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/c2cd2-p-ser184gly (accessed [today's date]).

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