Is C2 p.Asn471= (c.1413C>T) pathogenic?

C2 p.Asn471= (c.1413C>T) is classified Conflicting classifications of pathogenicity in C2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-19). Rare (popmax 0.119%, afr); Associated with age related macular degeneration 14.

What condition is associated with C2 p.Asn471= (c.1413C>T)?

C2 p.Asn471= (c.1413C>T) is associated with age related macular degeneration 14, complement component 2 deficiency (ClinVar).

How common is C2 p.Asn471= (c.1413C>T) in the general population?

C2 p.Asn471= (c.1413C>T) is rare (popmax 0.119%, afr) (gnomAD).

C2 p.Asn471=

c.1413C>T · rs138221333 · VCV905958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.119%, afr)

Conditions

age related macular degeneration 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.114	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -3.8
Overall
CADD	13.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.119% African / African-American · 89/75,018 alleles

Filtering AF 0.0987% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0913%

Overall 0.0135% 218/1,613,032 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.119%	843
Middle Eastern	0.033%	3,031
Admixed American	0.0117%	8,576
Remaining individualsnot grpmax-eligible	0.0096%	10,416
European (non-Finnish)	0.00898%	11,132
South Asian	0.00549%	18,217
East Asian	0.00446%	22,443
Finnishnot grpmax-eligible	0.00159%	62,924

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: C2
Protein: p.Asn471=
Coding: c.1413C>T
MANE Select: NM_000063
dbSNP: rs138221333
Type: single nucleotide variant
Location: chr6:31943277 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 471: a disulfide bond; the peptidase s1 domain; a β-strand

Full C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: complement component 2 deficiency

Similar variants

C2 c.1902+5G>A Uncertain significance ★★ same condition
C2 p.Arg129His Uncertain significance ★★ same condition
C2 p.Arg734Leu Uncertain significance ★★ ⚠ same condition
C2 p.Asp390Ala Uncertain significance ★★ ⚠ same condition
C2 p.Asp661Asn Uncertain significance ★★ ⚠ same condition
C2 p.Lys572Asn Uncertain significance ★★ ⚠ same condition
C2 p.Phe273= Uncertain significance ★★ same condition
C2 p.Phe95Val 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/c2-p-asn471 (accessed [today's date]).

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