Is C2 p.Ile30= (c.90C>A) pathogenic?

C2 p.Ile30= (c.90C>A) is classified Likely benign in C2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-28). Rare (popmax 0.158%, sas).

How common is C2 p.Ile30= (c.90C>A) in the general population?

C2 p.Ile30= (c.90C>A) is rare (popmax 0.158%, sas) (gnomAD).

C2 p.Ile30=

c.90C>A · rs561819885 · VCV1563705

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.158%, sas)

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 1.3	GERP -0.62, phastCons 0.77
Overall
CADD	11.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.158% South Asian · 144/91,082 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.0103% 167/1,614,210 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.158%	633
Remaining individualsnot grpmax-eligible	0.0288%	3,473
Middle Eastern	0.0165%	6,062
East Asian	0.00891%	11,221

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.Ile30=
Coding: c.90C>A
MANE Select: NM_000063
dbSNP: rs561819885
Type: single nucleotide variant
Location: chr6:31927998 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 30: a disulfide bond; the sushi 1 domain

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

Similar variants

C2 p.Ile30Met Uncertain significance ★ ⚠ same residue
C2 c.1902+5G>A Uncertain significance ★★ same type
C2 c.2029+5G>A Uncertain significance ★★ same type
C2 p.Ala363Thr Uncertain significance ★★ ⚠ same type
C2 p.Ala682Glu Uncertain significance ★★ ⚠ same type
C2 p.Arg124Gln Uncertain significance ★★ ⚠ same type
C2 p.Arg129His Uncertain significance ★★ same type
C2 p.Arg174Cys 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/c2-p-ile30 (accessed [today's date]).

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