Is C2 p.Ile484Val (c.1450A>G) pathogenic?

C2 p.Ile484Val (c.1450A>G) is classified Conflicting classifications of pathogenicity in C2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1352); Very rare (popmax 0.00833%, amr); Associated with age related macular degeneration 14.

What condition is associated with C2 p.Ile484Val (c.1450A>G)?

C2 p.Ile484Val (c.1450A>G) is associated with age related macular degeneration 14, complement component 2 deficiency (ClinVar).

How common is C2 p.Ile484Val (c.1450A>G) in the general population?

C2 p.Ile484Val (c.1450A>G) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about C2 p.Ile484Val (c.1450A>G)?

AlphaMissense predicts likely benign (score 0.1352) — an in-silico prediction, not a clinical call.

C2 p.Ile484Val

c.1450A>G · rs145988012 · VCV356250

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1352 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

age related macular degeneration 14

Computational evidence

Protein change
AlphaMissense	0.1352	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -6.85	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 3.6	GERP -0.32, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 18 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	17.49	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 0.00833% Admixed American · 5/60,012 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.0221% 357/1,612,598 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.824%	121
Remaining individualsnot grpmax-eligible	0.0576%	1,735
Admixed Americangrpmax	0.00833%	12,002
European (non-Finnish)	0.00593%	16,853
African / African-American	0.00267%	37,461

Ashkenazi Jewish 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: C2
Protein: p.Ile484Val
Coding: c.1450A>G
MANE Select: NM_000063
dbSNP: rs145988012
Type: single nucleotide variant
Location: chr6:31943314 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 484: 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-ile484val (accessed [today's date]).

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