Is C8G p.Ser18= (c.54G>A) pathogenic?

C8G p.Ser18= (c.54G>A) is classified Likely benign in C8G (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-01). Ultra-rare (popmax 0.0111%, eas); Associated with C8G-related disorder.

What condition is associated with C8G p.Ser18= (c.54G>A)?

C8G p.Ser18= (c.54G>A) is associated with C8G-related disorder (ClinVar).

How common is C8G p.Ser18= (c.54G>A) in the general population?

C8G p.Ser18= (c.54G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

C8G p.Ser18=

c.54G>A · rs550971839 · VCV3057776

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

C8G-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -2.8
Overall
CADD	4.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,872 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000496% 8/1,612,608 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,974
Admixed American	0.00167%	59,960
Remaining individualsnot grpmax-eligible	0.0016%	62,454
African / African-American	0.00133%	75,044

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.Ser18=
Coding: c.54G>A
MANE Select: NM_000606
dbSNP: rs550971839
Type: single nucleotide variant
Location: chr9:136945374 (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 p.Ser18Leu Uncertain significance ★ ⚠ same residue
C8G c.276-10G>A Likely 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.Tyr151= Likely benign same condition
C8G p.Tyr185= Benign same condition
C8G c.276-3dup 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-ser18 (accessed [today's date]).

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