Is C3 p.Lys155Gln (c.463A>C) pathogenic?

C3 p.Lys155Gln (c.463A>C) is classified Conflicting classifications of pathogenicity in C3 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.092); Rare (popmax 0.489%, nfe); Associated with complement component 3 deficiency.

What condition is associated with C3 p.Lys155Gln (c.463A>C)?

C3 p.Lys155Gln (c.463A>C) is associated with complement component 3 deficiency, age related macular degeneration 9, atypical hemolytic-uremic syndrome with C3 anomaly (ClinVar).

How common is C3 p.Lys155Gln (c.463A>C) in the general population?

C3 p.Lys155Gln (c.463A>C) is rare (popmax 0.489%, nfe) (gnomAD).

How is Complement component 3 deficiency inherited?

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

What do computational predictors say about C3 p.Lys155Gln (c.463A>C)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

C3 p.Lys155Gln

c.463A>C · rs147859257 · VCV92162

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.489%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complement component 3 deficiency

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -4.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.77	GERP -3.2
Regional constraint	o/e 0.74	unconstrained · MANE · 35 kb · p 3.5e-28 · regional, not allelic
Overall
CADD	11.09	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 0.489% European (non-Finnish) · 5,776/1,179,994 alleles

Filtering AF 0.479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.475%

Overall 0.379% 6,125/1,614,084 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.489%	204
Remaining individualsnot grpmax-eligible	0.261%	383
Finnishnot grpmax-eligible	0.122%	821
Amishnot grpmax-eligible	0.11%	910
Ashkenazi Jewishnot grpmax-eligible	0.105%	955
Admixed American	0.065%	1,539
African / African-American	0.048%	2,083
South Asian	0.0011%	91,080

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: C3
Protein: p.Lys155Gln
Coding: c.463A>C
MANE Select: NM_000064
dbSNP: rs147859257
Type: single nucleotide variant
Location: chr19:6718135 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 155: a UniProt-annotated variant site (in armd9; results in resistance to proteolytic inactivation by cfh and cfi)

Full C3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component 3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: age related macular degeneration 9 atypical hemolytic-uremic syndrome with C3 anomaly C3 glomerulonephritis atypical hemolytic-uremic syndrome inherited retinal dystrophy

For Complement component 3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

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C3 p.Arg161Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
C3 p.Arg592Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
C3 p.Arg592Trp Likely pathogenic ★★ ⚠ same condition
C3 p.Arg764Ter Pathogenic/Likely pathogenic ★★ same condition
C3 p.Ile1157Thr Pathogenic/Likely pathogenic ★★ ⚠ 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/c3-p-lys155gln (accessed [today's date]).

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