Is C8B p.Gly117Arg (c.349G>A) pathogenic?

C8B p.Gly117Arg (c.349G>A) is classified Benign/Likely benign in C8B (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0422); Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with type II complement component 8 deficiency.

What condition is associated with C8B p.Gly117Arg (c.349G>A)?

C8B p.Gly117Arg (c.349G>A) is associated with type II complement component 8 deficiency (ClinVar).

What do computational predictors say about C8B p.Gly117Arg (c.349G>A)?

AlphaMissense predicts likely benign (score 0.0422) — an in-silico prediction, not a clinical call.

C8B p.Gly117Arg

Q: How common is C8B p.Gly117Arg (c.349G>A) in the general population?

C8B p.Gly117Arg (c.349G>A) is common (popmax 100%, eas) — 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.349G>A · rs1013579 · VCV1169777

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0422 · ACMG-weighted

gnomAD v4.1

Common

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

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

type II complement component 8 deficiency

Computational evidence

Protein change
AlphaMissense	0.0422	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -4.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -3.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 37 kb · p 0.016 · regional, not allelic
Overall
CADD	9.755	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,835/44,840 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 97.3% 1,570,921/1,614,046 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Amishnot grpmax-eligible	99.7%	1
African / African-American	99.5%	1
South Asian	98.8%	1
Finnishnot grpmax-eligible	98.1%	1
Admixed American	97.4%	1
Remaining individualsnot grpmax-eligible	97.4%	1
Ashkenazi Jewishnot grpmax-eligible	97.2%	1
European (non-Finnish)	96.9%	1
Middle Eastern	96.8%	1

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: C8B
Protein: p.Gly117Arg
Coding: c.349G>A
MANE Select: NM_000066
dbSNP: rs1013579
Type: single nucleotide variant
Location: chr1:56956811 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 117: a UniProt-annotated variant site (in c8d2); a UniProt-annotated variant site (in allotype c8b b); the tsp type-1 1 domain

Full C8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

type II 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

C8B p.Gly117Glu Uncertain significance ★ ⚠ same residue
C8B p.Arg284Ter Pathogenic ★★ same condition
C8B p.Arg428Ter Pathogenic ★★ same condition
C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same condition
C8B p.Trp9Ter Pathogenic ★★ same condition
C8B p.Ala461Ser Uncertain significance ★★ ⚠ same condition
C8B p.Ala480Thr Uncertain significance ★★ ⚠ same condition
C8B p.Arg136His 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/c8b-p-gly117arg (accessed [today's date]).

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