Is C7 p.Arg402Ter (c.1204C>T) pathogenic?

C7 p.Arg402Ter (c.1204C>T) is classified Pathogenic/Likely pathogenic in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-01). Very rare (popmax 0.00167%, amr); Associated with C7-related disorder.

What condition is associated with C7 p.Arg402Ter (c.1204C>T)?

C7 p.Arg402Ter (c.1204C>T) is associated with C7-related disorder (ClinVar).

How common is C7 p.Arg402Ter (c.1204C>T) in the general population?

C7 p.Arg402Ter (c.1204C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

C7 p.Arg402Ter

c.1204C>T · rs200365542 · VCV1948673

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

C7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.66	GERP -0.46, phastCons 0.089
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,948 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000992% 16/1,613,336 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,948
European (non-Finnish)	0.00119%	84,252
South Asian	0.0011%	90,978

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: C7
Protein: p.Arg402Ter
Coding: c.1204C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs200365542
Type: single nucleotide variant
Location: chr5:40955497 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

Full C7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C7-related disorder

Similar variants

C7 p.Arg402Gln Uncertain significance ★★ ⚠ same residue
C7 c.739-2A>G Likely pathogenic ★★ same condition
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
C7 p.Asn494Lys Uncertain significance ★★ ⚠ same condition
C7 c.2166-1G>A Likely pathogenic ★ same condition
C7 c.982+2T>C Likely pathogenic ★ same condition
C7 p.Gln367Ter Likely pathogenic ★ same condition
C7 p.Gln461Ter Likely pathogenic ★ 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/c7-p-arg402ter (accessed [today's date]).

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