Is C2 p.Thr361Met (c.1082C>T) pathogenic?

C2 p.Thr361Met (c.1082C>T) is classified Uncertain significance in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1031); Very rare (popmax 0.00549%, sas); Associated with complement component 2 deficiency.

What condition is associated with C2 p.Thr361Met (c.1082C>T)?

C2 p.Thr361Met (c.1082C>T) is associated with complement component 2 deficiency, age related macular degeneration 14 (ClinVar).

How common is C2 p.Thr361Met (c.1082C>T) in the general population?

C2 p.Thr361Met (c.1082C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about C2 p.Thr361Met (c.1082C>T)?

AlphaMissense predicts likely benign (score 0.1031) — an in-silico prediction, not a clinical call.

C2 p.Thr361Met

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.

c.1082C>T · rs61730574 · VCV905441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1031 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

complement component 2 deficiency

Computational evidence

Protein change
AlphaMissense	0.1031	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.55	GERP 1.8
Regional constraint	o/e 0.84	unconstrained · MANE · 18 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	18.31	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 0.00549% South Asian · 5/91,078 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00062% 10/1,612,562 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
Admixed American	0.00167%	59,952
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.000254%	393,331

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.Thr361Met
Coding: c.1082C>T
dbSNP: rs61730574
Type: single nucleotide variant
Location: chr6:31937412 (GRCh38)

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

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-thr361met (accessed [today's date]).

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