Is C5 p.Gln19Ter (c.55C>T) pathogenic?

C5 p.Gln19Ter (c.55C>T) is classified Pathogenic in C5 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-22). Rare (popmax 0.145%, afr); Associated with C5-related disorders.

What condition is associated with C5 p.Gln19Ter (c.55C>T)?

C5 p.Gln19Ter (c.55C>T) is associated with C5-related disorders, lathosterolosis, complement component 5 deficiency (ClinVar).

How common is C5 p.Gln19Ter (c.55C>T) in the general population?

C5 p.Gln19Ter (c.55C>T) is rare (popmax 0.145%, afr) (gnomAD).

C5 p.Gln19Ter

c.55C>T · rs121909587 · VCV17050

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.145%, afr)

Conditions

C5-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 41
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	38.0	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 0.145% African / African-American · 109/75,014 alleles

Filtering AF 0.123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.115%

Overall 0.00793% 128/1,613,268 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.145%	688
Admixed American	0.0167%	6,002
Remaining individualsnot grpmax-eligible	0.0112%	8,924
South Asian	0.0011%	91,078
European (non-Finnish)	8.48e-05%	1,179,284

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: C5
Protein: p.Gln19Ter
Coding: c.55C>T
MANE Select: NM_001735
dbSNP: rs121909587
Type: single nucleotide variant
Location: chr9:121050192 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 19: a UniProt-annotated variant site (in c5d)

Full C5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C5-related disorders

Also linked: lathosterolosis complement component 5 deficiency

Similar variants

C5 c.2257+1G>A Likely pathogenic ★★ same condition
C5 c.4679-2A>G Likely pathogenic ★★ same condition
C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same condition
C5 p.Glu1437Ter Pathogenic/Likely pathogenic ★★ same condition
C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same condition
C5 c.2059+3A>G Uncertain significance ★★ same condition
C5 c.4081-6A>G Uncertain significance ★★ same condition
C5 c.4504+4A>G Uncertain significance ★★ 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/c5-p-gln19ter (accessed [today's date]).

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