Is C2 p.His369= (c.1107T>C) pathogenic?

C2 p.His369= (c.1107T>C) is classified Likely benign in C2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). Very rare (popmax 0.00659%, sas).

How common is C2 p.His369= (c.1107T>C) in the general population?

C2 p.His369= (c.1107T>C) is very rare (popmax 0.00659%, sas) (gnomAD).

C2 p.His369=

c.1107T>C · rs553732141 · VCV1080807

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.505	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Overall
CADD	0.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,080 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000868% 14/1,612,818 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
East Asian	0.00223%	44,790
European (non-Finnish)	0.000593%	168,569

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.His369=
Coding: c.1107T>C
MANE Select: NM_000063
dbSNP: rs553732141
Type: single nucleotide variant
Location: chr6:31937437 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 369: the vwfa domain; a β-strand

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

Similar variants

C2 p.His369Arg Uncertain significance ★ ⚠ same residue
C2 p.His369Asn 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

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-his369 (accessed [today's date]).

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