Is C2CD3 p.Thr558fs (c.1671dup) pathogenic?

C2CD3 p.Thr558fs (c.1671dup) is classified Pathogenic in C2CD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). Absent from gnomAD.

How common is C2CD3 p.Thr558fs (c.1671dup) in the general population?

C2CD3 p.Thr558fs (c.1671dup) is absent from gnomAD (gnomAD).

C2CD3 p.Thr558fs

c.1671dup · rs2496492248 · VCV2824597

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -0.52, phastCons 0.97

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C2CD3
Protein: p.Thr558fs
Coding: c.1671dup
MANE Select: NM_001286577
dbSNP: rs2496492248
Type: Duplication
Location: chr11:74114442 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 558: the c2 1 domain; the 'disordered' region

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

Similar variants

C2CD3 p.His904fs Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Val332fs Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Ala1017fs Pathogenic ★ same type
C2CD3 p.Arg18fs Pathogenic ★ same type
C2CD3 p.Asn1154fs Pathogenic ★ same type
C2CD3 p.Asn1427fs Pathogenic ★ same type
C2CD3 p.Cys1281fs Pathogenic ★ same type
C2CD3 p.Cys1867fs Likely pathogenic ★ 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-thr558fs (accessed [today's date]).

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