Is C8G p.Thr6fs (c.12del) pathogenic?

C8G p.Thr6fs (c.12del) is classified Likely benign in C8G (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-31). Low-frequency (popmax 1.08%, eas); Associated with C8G-related disorder.

What condition is associated with C8G p.Thr6fs (c.12del)?

C8G p.Thr6fs (c.12del) is associated with C8G-related disorder (ClinVar).

How common is C8G p.Thr6fs (c.12del) in the general population?

C8G p.Thr6fs (c.12del) is low-frequency (popmax 1.08%, eas) (gnomAD).

C8G p.Thr6fs

c.12del · rs60286503 · VCV3058784

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, eas)

Conditions

C8G-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 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.4	GERP -1.1
Overall
CADD	18.44	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 1.08% East Asian · 484/44,778 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.97%

Overall 0.0316% 508/1,609,884 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.08%	93
Remaining individualsnot grpmax-eligible	0.0241%	4,153
African / African-American	0.00133%	74,996
European (non-Finnish)	0.000679%	147,247

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: C8G
Protein: p.Thr6fs
Coding: c.12del
MANE Select: NM_000606
dbSNP: rs60286503
Type: Deletion
Location: chr9:136945332 (GRCh38)
Gene constraint: LOEUF 1.809 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.06 · 15 PDB

Full C8G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C8G-related disorder

Similar variants

C8G c.276-10G>A Likely benign same condition
C8G c.276-3dup Benign same condition
C8G c.*5G>A Likely benign same condition
C8G p.Ala70= Likely benign same condition
C8G p.Ser154= Likely benign same condition
C8G p.Ser18= Likely benign same condition
C8G p.Tyr151= Likely benign same condition
C8G p.Tyr185= Benign 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/c8g-p-thr6fs (accessed [today's date]).

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