Is C6 p.Ser813fs (c.2436_2440del) pathogenic?

C6 p.Ser813fs (c.24362440del) is classified Pathogenic/Likely pathogenic in C6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-30). Very rare (popmax 0.00133%, afr); Associated with C6-related disorders.

What condition is associated with C6 p.Ser813fs (c.2436_2440del)?

C6 p.Ser813fs (c.2436_2440del) is associated with C6-related disorders (ClinVar).

How common is C6 p.Ser813fs (c.2436_2440del) in the general population?

C6 p.Ser813fs (c.2436_2440del) is very rare (popmax 0.00133%, afr) (gnomAD).

C6 p.Ser813fs

c.2436_2440del · rs777936780 · VCV2975647

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

C6-related disorders

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 17 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,018 alleles

Overall 0.000205% 3/1,461,762 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,249
African / African-Americangrpmax	0.00133%	75,018

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: C6
Protein: p.Ser813fs
Coding: c.2436_2440del
MANE Select: NM_000065
dbSNP: rs777936780
Type: Deletion
Location: chr5:41149424 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 813: the kazal-like 1 domain; the 'c5b-binding domain' region; the 'factor i module (fim) 1' region; a β-strand; a disulfide bond

Full C6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C6-related disorders

Similar variants

C6 p.Asp627fs Likely pathogenic ★★ same condition
C6 p.Gln111fs Likely pathogenic ★ same condition
C6 p.Gln268Ter Likely pathogenic ★ same condition
C6 c.-3G>A Likely benign same condition
C6 p.Arg289= Likely benign same condition
C6 p.Gln274fs Pathogenic/Likely pathogenic ★★ same type
C6 p.Gln380fs Pathogenic/Likely pathogenic ★★ same type
C6 p.Gln779fs Pathogenic/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/c6-p-ser813fs (accessed [today's date]).

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