Is C8A p.Tyr210Ter (c.630C>A) pathogenic?

C8A p.Tyr210Ter (c.630C>A) is classified Pathogenic/Likely pathogenic in C8A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-19). Ultra-rare (popmax 0.052%, mid); Associated with type I complement component 8 deficiency.

What condition is associated with C8A p.Tyr210Ter (c.630C>A)?

C8A p.Tyr210Ter (c.630C>A) is associated with type I complement component 8 deficiency (ClinVar).

How common is C8A p.Tyr210Ter (c.630C>A) in the general population?

C8A p.Tyr210Ter (c.630C>A) is ultra-rare (popmax 0.052%, mid) (gnomAD).

C8A p.Tyr210Ter

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.630C>A · rs748306602 · VCV1028843

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, mid)

Conditions

type I complement component 8 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.96, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.052% Middle Eastern · 3/5,774 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00753%

Overall 0.000806% 13/1,613,416 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.052%	1,925
South Asian	0.0022%	45,532
Remaining individualsnot grpmax-eligible	0.0016%	62,448
African / African-American	0.00133%	75,008
European (non-Finnish)	0.000509%	196,619

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.Tyr210Ter
Coding: c.630C>A
MANE Select: NM_000562
dbSNP: rs748306602
Type: single nucleotide variant
Location: chr1:56881610 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58 · 11 PDB
Residue 210: 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.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
C8A p.Asp202= 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-tyr210ter (accessed [today's date]).

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