Is C2 p.Ser266= (c.798G>A) pathogenic?

C2 p.Ser266= (c.798G>A) is classified Likely benign in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). Very rare (popmax 0.0022%, sas).

How common is C2 p.Ser266= (c.798G>A) in the general population?

C2 p.Ser266= (c.798G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

C2 p.Ser266=

c.798G>A · rs1324146336 · VCV1532164

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, 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 -5.4	GERP -3.5
Overall
CADD	0.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000558% 9/1,613,944 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
Admixed American	0.00167%	59,980
African / African-American	0.00134%	74,900
European (non-Finnish)	0.000424%	235,995

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.Ser266=
Coding: c.798G>A
MANE Select: NM_000063
dbSNP: rs1324146336
Type: single nucleotide variant
Location: chr6:31934248 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 266: the vwfa domain

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

Similar variants

C2 p.Ser266Leu Uncertain significance ★ ⚠ same residue
C2 p.Ser266Trp Uncertain significance ★ ⚠ same residue
C2 p.Ser266fs Pathogenic ★ 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

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-ser266 (accessed [today's date]).

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