Is RBP1 p.Pro43= (c.129C>T) pathogenic?

RBP1 p.Pro43= (c.129C>T) is classified Likely benign in RBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-27). Ultra-rare (popmax 0.0166%, mid).

How common is RBP1 p.Pro43= (c.129C>T) in the general population?

RBP1 p.Pro43= (c.129C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

RBP1 p.Pro43=

c.129C>T · rs1435499551 · VCV1660694

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.4	GERP -2.9, phastCons 0.001
Overall
CADD	5.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,018 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000254% 4/1,577,446 alleles · ultra-rare exomes 4/1,425,084 · genomes 0/152,362 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,018
African / African-American	0.00136%	73,698
European (non-Finnish)	0.000172%	581,142

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: RBP1
Protein: p.Pro43=
Coding: c.129C>T
MANE Select: NM_002899
dbSNP: rs1435499551
Type: single nucleotide variant
Location: chr3:139539590 (GRCh38)

Full RBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/rbp1-p-pro43 (accessed [today's date]).

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