Is C6 p.Tyr810fs (c.2428dup) pathogenic?

C6 p.Tyr810fs (c.2428dup) is classified Pathogenic/Likely pathogenic in C6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-15). Very rare (popmax 0.000169%, nfe).

How common is C6 p.Tyr810fs (c.2428dup) in the general population?

C6 p.Tyr810fs (c.2428dup) is very rare (popmax 0.000169%, nfe) (gnomAD).

C6 p.Tyr810fs

c.2428dup · VCV4780989

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 0.000169%, nfe)

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 2.9	GERP 0.62, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,950 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,782 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: C6
Protein: p.Tyr810fs
Coding: c.2428dup
MANE Select: NM_000065
Type: Duplication
Location: chr5:41149435 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 810: 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

Similar variants

C6 p.Tyr451Ter Pathogenic/Likely pathogenic ★★ same type
C6 p.Asn808fs Pathogenic ★ same type
C6 p.Cys93fs Pathogenic ★ same type
C6 p.Tyr285fs 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-tyr810fs (accessed [today's date]).

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