Is C5 p.Lys372Arg (c.1115A>G) pathogenic?

C5 p.Lys372Arg (c.1115A>G) is classified Pathogenic in C5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2005-04-01). AlphaMissense: likely benign (0.0989); Absent from gnomAD v4.1; Associated with complement component 5 deficiency.

What condition is associated with C5 p.Lys372Arg (c.1115A>G)?

C5 p.Lys372Arg (c.1115A>G) is associated with complement component 5 deficiency (ClinVar).

How common is C5 p.Lys372Arg (c.1115A>G) in the general population?

C5 p.Lys372Arg (c.1115A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C5 p.Lys372Arg (c.1115A>G)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

C5 p.Lys372Arg

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1115A>G · rs587776846 · VCV17053

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,582,410)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement component 5 deficiency

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign ⚠ discordant with ClinVar
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.95	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.67	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.2	GERP 0.43, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,582,410). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C5
Protein: p.Lys372Arg
Coding: c.1115A>G
MANE Select: NM_001735
dbSNP: rs587776846
Type: single nucleotide variant
Location: chr9:121023405 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 372: 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

complement component 5 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

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.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
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-lys372arg (accessed [today's date]).

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