Is C8A p.Asp202= (c.606T>C) pathogenic?

C8A p.Asp202= (c.606T>C) is classified Likely benign in C8A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-24). Rare (popmax 0.264%, nfe); Associated with type I complement component 8 deficiency.

What condition is associated with C8A p.Asp202= (c.606T>C)?

C8A p.Asp202= (c.606T>C) is associated with type I complement component 8 deficiency (ClinVar).

How common is C8A p.Asp202= (c.606T>C) in the general population?

C8A p.Asp202= (c.606T>C) is rare (popmax 0.264%, nfe) (gnomAD).

C8A p.Asp202=

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.606T>C · rs150755683 · VCV791416

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.264%, nfe)

Conditions

type I complement component 8 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 -2	GERP -3.8
Overall
CADD	4.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.264% European (non-Finnish) · 3,111/1,179,760 alleles

Filtering AF 0.256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.253%

Overall 0.208% 3,357/1,613,756 alleles · rare exomes 3,151/1,461,466 · genomes 206/152,290 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.264%	379
Remaining individualsnot grpmax-eligible	0.17%	589
Finnishnot grpmax-eligible	0.137%	728
African / African-American	0.0467%	2,143
Admixed American	0.0217%	4,615
Middle Eastern	0.0166%	6,008
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,798
South Asian	0.0011%	91,082

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: C8A
Protein: p.Asp202=
Coding: c.606T>C
MANE Select: NM_000562
dbSNP: rs150755683
Type: single nucleotide variant
Location: chr1:56881586 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58 · 11 PDB
Residue 202: an α-helix; the macpf domain

Full C8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

type I complement component 8 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

C8A p.Arg424Ter Pathogenic ★★ same condition
C8A p.Arg498Ter Pathogenic/Likely pathogenic ★★ same condition
C8A p.Tyr210Ter Pathogenic/Likely pathogenic ★★ same condition
C8A p.Tyr384Ter Pathogenic/Likely pathogenic ★★ same condition
C8A p.Ile441Val Uncertain significance ★★ ⚠ same condition
C8A p.Lys57Thr Uncertain significance ★★ ⚠ same condition
C8A p.Pro52Leu Uncertain significance ★★ ⚠ same condition
C8A p.Ala36Glu Benign/Likely benign ★★ 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/c8a-p-asp202 (accessed [today's date]).

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