Is CIITA p.Arg7Ser (c.19C>A) pathogenic?

CIITA p.Arg7Ser (c.19C>A) is classified Uncertain significance in CIITA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-15). AlphaMissense: likely benign (0.2297); Ultra-rare (popmax 0.0133%, amr); Associated with MHC class II deficiency.

What condition is associated with CIITA p.Arg7Ser (c.19C>A)?

CIITA p.Arg7Ser (c.19C>A) is associated with MHC class II deficiency (ClinVar).

How common is CIITA p.Arg7Ser (c.19C>A) in the general population?

CIITA p.Arg7Ser (c.19C>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CIITA p.Arg7Ser (c.19C>A)?

AlphaMissense predicts likely benign (score 0.2297) — an in-silico prediction, not a clinical call.

CIITA p.Arg7Ser

Q: How is Immunodeficiency by defective expression of MHC class II inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.19C>A · rs202176090 · VCV2179059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MHC class II deficiency

Computational evidence

Protein change
AlphaMissense	0.2297	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.36	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 0.16	GERP -3.8
Regional constraint	o/e 1.10	unconstrained · MANE · 46 kb · p 6.2e-05 · regional, not allelic
Overall
CADD	15.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,932 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000548% 8/1,460,976 alleles · ultra-rare

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: CIITA
Protein: p.Arg7Ser
Coding: c.19C>A
MANE Select: NM_000246
dbSNP: rs202176090
Type: single nucleotide variant
Location: chr16:10877349 (GRCh38)
Gene constraint: LOEUF 0.729 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.10

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

Disease context

MHC class II deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency by defective expression of MHC class II (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CIITA p.Arg7Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CIITA p.Arg7His Conflicting classifications of pathogenicity ★ ⚠ same residue
CIITA p.Arg7= Likely benign ★ same residue
CIITA c.199+1G>A Likely pathogenic ★★ same condition
CIITA c.2888+1G>A Pathogenic/Likely pathogenic ★★ same condition
CIITA c.2889-1G>T Pathogenic/Likely pathogenic ★★ same condition
CIITA c.436+1G>A Likely pathogenic ★★ same condition
CIITA c.628+1G>A Likely pathogenic ★★ 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/ciita-p-arg7ser (accessed [today's date]).

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