Is C5 p.Asp264= (c.792C>T) pathogenic?

C5 p.Asp264= (c.792C>T) is classified Likely benign in C5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-21). Very rare (popmax 0.00445%, sas); Associated with Eculizumab, poor response to.

What condition is associated with C5 p.Asp264= (c.792C>T)?

C5 p.Asp264= (c.792C>T) is associated with Eculizumab, poor response to, complement component 5 deficiency (ClinVar).

How common is C5 p.Asp264= (c.792C>T) in the general population?

C5 p.Asp264= (c.792C>T) is very rare (popmax 0.00445%, sas) (gnomAD).

C5 p.Asp264=

c.792C>T · rs751759129 · VCV1539157

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00445%, sas)

Conditions

Eculizumab, poor response to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.2	GERP -3.1
Overall
CADD	0.632	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% South Asian · 4/89,890 alleles

Filtering AF 0.00144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00132% 21/1,586,556 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00445%	22,473
European (non-Finnish)	0.00138%	72,307
African / African-American	0.00134%	74,386

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.Asp264=
Coding: c.792C>T
MANE Select: NM_001735
dbSNP: rs751759129
Type: single nucleotide variant
Location: chr9:121027241 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 264: a UniProt-annotated variant site (in c5d); a β-strand

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.Asp264Asn Uncertain significance ★ ⚠ 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-asp264 (accessed [today's date]).

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