Is RARB p.Pro429= (c.1287T>C) pathogenic?

RARB p.Pro429= (c.1287T>C) is classified Likely benign in RARB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Very rare (popmax 0.00119%, nfe).

How common is RARB p.Pro429= (c.1287T>C) in the general population?

RARB p.Pro429= (c.1287T>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

RARB p.Pro429=

c.1287T>C · VCV4961531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

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 2.2	GERP 0.004, phastCons 1
Overall
CADD	9.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,814 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,613,778 alleles · very rare exomes 12/1,461,616 · genomes 3/152,162 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)grpmax	0.00119%	84,272

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RARB
Protein: p.Pro429=
Coding: c.1287T>C
MANE Select: NM_000965
Type: single nucleotide variant
Location: chr3:25596556 (GRCh38)
Gene constraint: LOEUF 0.477 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 80.68 · 9 PDB
Residue 429: the 'disordered' region

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

Similar variants

RARB p.Arg387Cys Pathogenic/Likely pathogenic ★★ same type
RARB p.Gln404Ter Pathogenic/Likely pathogenic ★★ same type
RARB p.Gly282Ser Pathogenic/Likely pathogenic ★★ same type
RARB p.Gly384Asp Likely pathogenic ★★ same type
RARB p.Leu213Pro Pathogenic/Likely pathogenic ★★ same type
RARB p.Leu407Pro Likely pathogenic ★★ same type
RARB p.Ser398Ter Pathogenic/Likely pathogenic ★★ same type
RARB p.Arg137Ter Uncertain significance ★★ same type

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/rarb-p-pro429 (accessed [today's date]).

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