Is RFXANK p.Pro44= (c.132C>T) pathogenic?

RFXANK p.Pro44= (c.132C>T) is classified Likely benign in RFXANK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0845%, sas); Associated with MHC class II deficiency.

What condition is associated with RFXANK p.Pro44= (c.132C>T)?

RFXANK p.Pro44= (c.132C>T) is associated with MHC class II deficiency (ClinVar).

How common is RFXANK p.Pro44= (c.132C>T) in the general population?

RFXANK p.Pro44= (c.132C>T) is ultra-rare (popmax 0.0845%, sas) (gnomAD).

RFXANK p.Pro44=

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.132C>T · rs745351660 · VCV764079

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0845%, sas)

Conditions

MHC class II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -2.4, phastCons 0.081
Overall
CADD	8.362	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0845% South Asian · 77/91,094 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00508% 82/1,614,102 alleles · ultra-rare exomes 80/1,461,892 · genomes 2/152,210 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0845%	1,183
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-American	0.00133%	74,920
European (non-Finnish)	0.000169%	590,030

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: RFXANK
Protein: p.Pro44=
Coding: c.132C>T
MANE Select: NM_003721
dbSNP: rs745351660
Type: single nucleotide variant
Location: chr19:19194078 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.90 · 3 PDB
Residue 44: the 'disordered' region

Full RFXANK 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

RFXANK c.271+1G>C Pathogenic/Likely pathogenic ★★ same condition
RFXANK c.438+1G>T Pathogenic/Likely pathogenic ★★ same condition
RFXANK p.Arg212Ter Pathogenic ★★ same condition
RFXANK p.Arg78Ter Pathogenic/Likely pathogenic ★★ same condition
RFXANK p.Asp121Val Pathogenic/Likely pathogenic ★★ same condition
RFXANK p.Tyr186Ter Pathogenic/Likely pathogenic ★★ same condition
RFXANK c.337+5G>A Uncertain significance ★★ same condition
RFXANK c.438+4C>T 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/rfxank-p-pro44 (accessed [today's date]).

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