Is C5 p.Lys115Glu (c.343A>G) pathogenic?

C5 p.Lys115Glu (c.343A>G) is classified Uncertain significance in C5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). AlphaMissense: likely benign (0.1641); Ultra-rare (popmax 0.0156%, eas).

How common is C5 p.Lys115Glu (c.343A>G) in the general population?

C5 p.Lys115Glu (c.343A>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about C5 p.Lys115Glu (c.343A>G)?

AlphaMissense predicts likely benign (score 0.1641) — an in-silico prediction, not a clinical call.

C5 p.Lys115Glu

c.343A>G · rs750310964 · VCV1921538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1641	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -10.20	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP 1.7, phastCons 0.49
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	19.52	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

Grpmax group 0.0156% East Asian · 7/44,756 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.000558% 9/1,613,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,394
South Asian	0.0011%	91,066
European (non-Finnish)	8.48e-05%	1,179,350

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.Lys115Glu
Coding: c.343A>G
MANE Select: NM_001735
dbSNP: rs750310964
Type: single nucleotide variant
Location: chr9:121043082 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 115: a UniProt-annotated variant site (in c5d); a β-strand

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

Similar variants

C5 c.2257+1G>A Likely pathogenic ★★ same type
C5 c.4679-2A>G Likely pathogenic ★★ same type
C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same type
C5 p.Gln19Ter Pathogenic ★★ same type
C5 p.Glu1437Ter Pathogenic/Likely pathogenic ★★ same type
C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same type
C5 c.2059+3A>G Uncertain significance ★★ same type
C5 c.3391-13T>A Uncertain significance ★★ same type

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-lys115glu (accessed [today's date]).

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