Is C5 p.Thr429= (c.1287G>A) pathogenic?

C5 p.Thr429= (c.1287G>A) is classified Benign/Likely benign in C5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.303%, afr); Associated with Eculizumab, poor response to.

What condition is associated with C5 p.Thr429= (c.1287G>A)?

C5 p.Thr429= (c.1287G>A) is associated with Eculizumab, poor response to, complement component 5 deficiency (ClinVar).

How common is C5 p.Thr429= (c.1287G>A) in the general population?

C5 p.Thr429= (c.1287G>A) is rare (popmax 0.303%, afr) (gnomAD).

C5 p.Thr429=

c.1287G>A · rs145139701 · VCV1170893

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.303%, afr)

Conditions

Eculizumab, poor response to

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 -7.1	GERP -3.4
Overall
CADD	0.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.303% African / African-American · 227/74,970 alleles

Filtering AF 0.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.258%

Overall 0.0174% 280/1,612,930 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.303%	330
Admixed American	0.0267%	3,751
Remaining individualsnot grpmax-eligible	0.016%	6,246
European (non-Finnish)	0.00221%	45,348
South Asian	0.0011%	91,050

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.Thr429=
Coding: c.1287G>A
MANE Select: NM_001735
dbSNP: rs145139701
Type: single nucleotide variant
Location: chr9:121021524 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 429: a β-strand; a UniProt-annotated variant site (in c5d)

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

Disease context

Eculizumab, poor response to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: complement component 5 deficiency

Similar variants

C5 p.Thr429Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
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.Gln19Ter 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

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-thr429 (accessed [today's date]).

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