Is C2 p.Pro207fs (c.620_621del) pathogenic?

C2 p.Pro207fs (c.620621del) is classified Likely pathogenic in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-12). Associated with C2-related disorder.

What condition is associated with C2 p.Pro207fs (c.620_621del)?

C2 p.Pro207fs (c.620_621del) is associated with C2-related disorder (ClinVar).

C2 p.Pro207fs

c.620_621del · VCV4974230

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

C2-related disorder

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 5 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.74	GERP -3.8

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

Variant & gene context

Gene: C2
Protein: p.Pro207fs
Coding: c.620_621del
MANE Select: NM_000063
Type: Deletion
Location: chr6:31933869 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 207: an α-helix

Full C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C2-related disorder

Similar variants

C2 c.841_849+19del Pathogenic/Likely pathogenic ★★ same condition
C2 p.Ala495fs Likely pathogenic ★ same condition
C2 p.Ser80fs Pathogenic ★ same condition
C2 p.Ser186Cys Uncertain significance ★ ⚠ same condition
ZBTB12 p.Ile80= Benign ★ same condition
C2 c.1455+17del Benign/Likely benign ★★ same type
C2 c.1567+22_1567+43del Benign/Likely benign ★★ same type
C2 c.1811-16del Benign/Likely benign ★★ 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/c2-p-pro207fs (accessed [today's date]).

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