Is C2 c.*120T>C pathogenic?

C2 c.120T>C is classified Uncertain significance in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with complement component 2 deficiency.

What condition is associated with C2 c.*120T>C?

C2 c.*120T>C is associated with complement component 2 deficiency, age related macular degeneration 14 (ClinVar).

How common is C2 c.*120T>C in the general population?

C2 c.*120T>C is absent from gnomAD v4.1 (gnomAD).

C2 c.*120T>C

Q: How is Immunodeficiency due to a classical component pathway complement deficiency inherited?

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

rs886061294 · VCV356263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

complement component 2 deficiency

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 0.063	GERP -2.8
Non-coding constraint	Z 5.28	1 kb window · o/e 0.65 · regional · uncalibrated
Overall
CADD	3.366	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C2
Coding: c.*120T>C
MANE Select: NM_000063
dbSNP: rs886061294
Type: single nucleotide variant
Location: chr6:31945477 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB

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

Disease context

complement component 2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: age related macular degeneration 14

For Immunodeficiency due to a classical component pathway complement deficiency (Orphanet):

Inheritance: Autosomal recessive

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-c-star-120t-c (accessed [today's date]).

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