Is C2 p.Asn513= (c.1539C>T) pathogenic?

C2 p.Asn513= (c.1539C>T) is classified Likely benign in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). Very rare (popmax 0.00549%, sas).

How common is C2 p.Asn513= (c.1539C>T) in the general population?

C2 p.Asn513= (c.1539C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

C2 p.Asn513=

c.1539C>T · VCV4692895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.041	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.093	GERP -3.2, phastCons 0.001
Overall
CADD	10.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,092 alleles

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

Overall 0.00149% 24/1,612,900 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00267%	37,469
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00127%	78,666

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.Asn513=
Coding: c.1539C>T
MANE Select: NM_000063
Type: single nucleotide variant
Location: chr6:31943499 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 513: a disulfide bond; the peptidase s1 domain

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

Similar variants

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
C2 p.Arg176Cys 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-asn513 (accessed [today's date]).

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