Is C5 p.Leu310= (c.928C>T) pathogenic?

C5 p.Leu310= (c.928C>T) is classified Likely benign in C5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-09). Ultra-rare (popmax 0.02%, nfe); Associated with complement component 5 deficiency.

What condition is associated with C5 p.Leu310= (c.928C>T)?

C5 p.Leu310= (c.928C>T) is associated with complement component 5 deficiency (ClinVar).

How common is C5 p.Leu310= (c.928C>T) in the general population?

C5 p.Leu310= (c.928C>T) is ultra-rare (popmax 0.02%, nfe) (gnomAD).

C5 p.Leu310=

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.928C>T · rs375870111 · VCV1575544

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, nfe)

Conditions

complement component 5 deficiency

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 0.41	GERP 0.84, phastCons 0.004
Overall
CADD	1.743	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% European (non-Finnish) · 236/1,179,606 alleles

Filtering AF 0.0179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0163% 263/1,612,668 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0272%	3,673
European (non-Finnish)grpmax	0.02%	4,998
East Asian	0.00893%	11,198
Admixed American	0.00501%	19,976
African / African-American	0.00268%	37,369
Finnishnot grpmax-eligible	0.00157%	63,528

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu310=
Coding: c.928C>T
MANE Select: NM_001735
dbSNP: rs375870111
Type: single nucleotide variant
Location: chr9:121025526 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 310: a UniProt-annotated variant site (in c5d); a turn

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 p.Leu310Arg 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-leu310 (accessed [today's date]).

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