Is C6 p.Asp627= (c.1881C>T) pathogenic?

C6 p.Asp627= (c.1881C>T) is classified Benign/Likely benign in C6 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele; Associated with complement component 6 deficiency.

What condition is associated with C6 p.Asp627= (c.1881C>T)?

C6 p.Asp627= (c.1881C>T) is associated with complement component 6 deficiency (ClinVar).

C6 p.Asp627=

Q: How common is C6 p.Asp627= (c.1881C>T) in the general population?

C6 p.Asp627= (c.1881C>T) is common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Immunodeficiency due to a late component of complement deficiency inherited?

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

c.1881C>T · rs6866352 · VCV1170114

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

complement component 6 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 0.033	GERP -3.8, phastCons 0.012
Overall
CADD	1.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% Middle Eastern · 6,032/6,032 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 100% 1,598,021/1,598,182 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
Middle Easterngrpmax	100%	1
South Asian	100%	1
African / African-American	100%	1
European (non-Finnish)	100%	1
Admixed American	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Remaining individualsnot grpmax-eligible	100%	1
East Asian	99.7%	1

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: C6
Protein: p.Asp627=
Coding: c.1881C>T
MANE Select: NM_000065
dbSNP: rs6866352
Type: single nucleotide variant
Location: chr5:41158761 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 627: the 'ccp 1' region; an α-helix

Full C6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component 6 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to a late component of complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Arg606Ter Pathogenic ★★ same condition
C6 p.Asp627fs Likely pathogenic ★★ same residue
C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Tyr683Ter Pathogenic/Likely pathogenic ★★ same condition
C6 p.Arg407Cys Uncertain significance ★★ same condition
C6 p.Arg48Lys Uncertain significance ★★ same condition
C6 p.Arg701Trp 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/c6-p-asp627 (accessed [today's date]).

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