Is C3 p.Val551= (c.1653G>T) pathogenic?

C3 p.Val551= (c.1653G>T) is classified Benign in C3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.09%, afr); Associated with age related macular degeneration 9.

What condition is associated with C3 p.Val551= (c.1653G>T)?

C3 p.Val551= (c.1653G>T) is associated with age related macular degeneration 9, atypical hemolytic-uremic syndrome with C3 anomaly, complement component 3 deficiency (ClinVar).

How common is C3 p.Val551= (c.1653G>T) in the general population?

C3 p.Val551= (c.1653G>T) is low-frequency (popmax 2.09%, afr) (gnomAD).

C3 p.Val551=

c.1653G>T · rs344534 · VCV330322

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, afr)

Conditions

age related macular degeneration 9

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 -0.46	GERP -3, phastCons 0.053
Overall
CADD	10.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% African / African-American · 1,570/75,024 alleles

Filtering AF 2.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.97%

Overall 0.111% 1,788/1,613,366 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.09%	48
Middle Eastern	0.132%	757
Remaining individualsnot grpmax-eligible	0.122%	822
Admixed American	0.108%	923
European (non-Finnish)	0.00585%	17,099

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.Val551=
Coding: c.1653G>T
MANE Select: NM_000064
dbSNP: rs344534
Type: single nucleotide variant
Location: chr19:6710672 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.84 · 80 PDB
Residue 551: a β-strand

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

Disease context

Also linked: atypical hemolytic-uremic syndrome with C3 anomaly complement component 3 deficiency

Similar variants

C3 p.Val551Ala Uncertain significance ★ ⚠ same residue
C3 p.Val551Met Uncertain significance ★ ⚠ same residue
C3 c.1003+1G>A Pathogenic/Likely pathogenic ★★ same condition
C3 c.2863+1G>T Likely pathogenic ★★ same condition
C3 c.4030-2A>G Likely pathogenic ★★ same condition
C3 p.Arg161Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
C3 p.Arg592Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
C3 p.Arg592Trp 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-val551 (accessed [today's date]).

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