Is C8A p.Ala36Glu (c.107C>A) pathogenic?

C8A p.Ala36Glu (c.107C>A) is classified Benign/Likely benign in C8A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1443); Common (popmax 11.2%, sas) — too common for a highly-penetrant pathogenic allele; Associated with type I complement component 8 deficiency.

What condition is associated with C8A p.Ala36Glu (c.107C>A)?

C8A p.Ala36Glu (c.107C>A) is associated with type I complement component 8 deficiency (ClinVar).

What do computational predictors say about C8A p.Ala36Glu (c.107C>A)?

AlphaMissense predicts likely benign (score 0.1443) — an in-silico prediction, not a clinical call.

C8A p.Ala36Glu

Q: How common is C8A p.Ala36Glu (c.107C>A) in the general population?

C8A p.Ala36Glu (c.107C>A) is common (popmax 11.2%, 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.107C>A · rs116201358 · VCV1164179

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1443 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.2%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

type I complement component 8 deficiency

Computational evidence

Protein change
AlphaMissense	0.1443	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 2.1, phastCons 0.34
Regional constraint	o/e 1.08	unconstrained · MANE · 63 kb · p 0.034 · regional, not allelic
Overall
CADD	21.5	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 11.2% South Asian · 10,164/91,040 alleles

Filtering AF 11% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.9%

Overall 1.37% 22,107/1,613,714 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	11.2%	9
Middle Eastern	1.9%	53
Ashkenazi Jewishnot grpmax-eligible	1.6%	63
Remaining individualsnot grpmax-eligible	1.47%	68
European (non-Finnish)	0.836%	120
Admixed American	0.342%	292
Finnishnot grpmax-eligible	0.339%	295
African / African-American	0.141%	708
East Asian	0.107%	934

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.Ala36Glu
Coding: c.107C>A
MANE Select: NM_000562
dbSNP: rs116201358
Type: single nucleotide variant
Location: chr1:56867638 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58 · 11 PDB
Residue 36: an α-helix

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.Ala36= Benign/Likely benign ★★ same residue
C8A p.Ala36Val Uncertain significance ★ ⚠ same residue
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

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-ala36glu (accessed [today's date]).

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