Is C8A p.Gln93Lys (c.277C>A) pathogenic?

C8A p.Gln93Lys (c.277C>A) is classified Benign/Likely benign in C8A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.071); Common (popmax 50.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with type I complement component 8 deficiency.

What condition is associated with C8A p.Gln93Lys (c.277C>A)?

C8A p.Gln93Lys (c.277C>A) is associated with type I complement component 8 deficiency (ClinVar).

What do computational predictors say about C8A p.Gln93Lys (c.277C>A)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

C8A p.Gln93Lys

Q: How common is C8A p.Gln93Lys (c.277C>A) in the general population?

C8A p.Gln93Lys (c.277C>A) is common (popmax 50.3%, sas) — 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.277C>A · rs652785 · VCV17039

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 50.3%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

type I complement component 8 deficiency

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.83	GERP 1.3, phastCons 0.25
Regional constraint	o/e 1.08	unconstrained · MANE · 63 kb · p 0.034 · regional, not allelic
Overall
CADD	7.544	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 50.3% South Asian · 45,751/91,004 alleles

Filtering AF 49.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.7%

Overall 37.6% 605,649/1,612,406 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	50.3%	2
Middle Eastern	44.8%	2
East Asian	42.4%	2
Ashkenazi Jewishnot grpmax-eligible	40.5%	2
European (non-Finnish)	38.3%	3
Remaining individualsnot grpmax-eligible	37.7%	3
Finnishnot grpmax-eligible	35.1%	3
Amishnot grpmax-eligible	31.9%	3
Admixed American	22.3%	4
African / African-American	20.8%	5

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.Gln93Lys
Coding: c.277C>A
MANE Select: NM_000562
dbSNP: rs652785
Type: single nucleotide variant
Location: chr1:56875054 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58 · 11 PDB
Residue 93: a UniProt-annotated variant site (in allele c8a*b)

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-gln93lys (accessed [today's date]).

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