Is RFX5 p.Pro129= (c.387A>G) pathogenic?

RFX5 p.Pro129= (c.387A>G) is classified Likely benign in RFX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Ultra-rare (popmax 0.029%, eas); Associated with MHC class II deficiency.

What condition is associated with RFX5 p.Pro129= (c.387A>G)?

RFX5 p.Pro129= (c.387A>G) is associated with MHC class II deficiency (ClinVar).

How common is RFX5 p.Pro129= (c.387A>G) in the general population?

RFX5 p.Pro129= (c.387A>G) is ultra-rare (popmax 0.029%, eas) (gnomAD).

RFX5 p.Pro129=

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.387A>G · rs200465567 · VCV1592817

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

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 -5.6	GERP -4.9
Overall
CADD	6.962	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,870 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00335% 54/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
Remaining individualsnot grpmax-eligible	0.0112%	8,930
South Asian	0.00549%	18,214
European (non-Finnish)	0.00229%	43,704
Admixed American	0.00167%	60,012
African / African-American	0.00133%	74,982

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: RFX5
Protein: p.Pro129=
Coding: c.387A>G
MANE Select: NM_001025603
dbSNP: rs200465567
Type: single nucleotide variant
Location: chr1:151344503 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.48 · 3 PDB
Residue 129: a DNA-binding region; an α-helix

Full RFX5 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

RFX5 p.Pro129Ser Uncertain significance ★ ⚠ same residue
RFX5 p.Pro129fs Pathogenic/Likely pathogenic ★★ same residue
RFX5 c.555+1G>A Likely pathogenic ★★ same condition
RFX5 c.757+1G>A Pathogenic/Likely pathogenic ★★ same condition
RFX5 p.Arg239Ter Pathogenic ★★ same condition
RFX5 p.Arg294Ter Pathogenic/Likely pathogenic ★★ same condition
RFX5 p.Arg35Ter Pathogenic/Likely pathogenic ★★ same condition
RFX5 c.474-3C>A 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/rfx5-p-pro129 (accessed [today's date]).

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