Is RBM8A p.Pro169= (c.507A>C) pathogenic?

RBM8A p.Pro169= (c.507A>C) is classified Likely benign in RBM8A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). Very rare (popmax 0.00449%, nfe); Associated with thrombocytopenia-absent radius syndrome.

What condition is associated with RBM8A p.Pro169= (c.507A>C)?

RBM8A p.Pro169= (c.507A>C) is associated with thrombocytopenia-absent radius syndrome (ClinVar).

How common is RBM8A p.Pro169= (c.507A>C) in the general population?

RBM8A p.Pro169= (c.507A>C) is very rare (popmax 0.00449%, nfe) (gnomAD).

RBM8A p.Pro169=

c.507A>C · VCV4752820

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Conditions

thrombocytopenia-absent radius syndrome

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 0.058	GERP 0.78, phastCons 0.97
Overall
CADD	11.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% European (non-Finnish) · 53/1,180,022 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00328% 53/1,614,108 alleles · very rare exomes 53/1,461,782 · genomes 0/152,326 · joint denominator

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: RBM8A
Protein: p.Pro169=
Coding: c.507A>C
MANE Select: NM_005105
Type: single nucleotide variant
Location: chr1:145925900 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 80.24 · 20 PDB
Residue 169: the 'disordered' region

Full RBM8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombocytopenia-absent radius syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBM8A p.Asn135Ser Uncertain significance ★★ ⚠ same condition
RBM8A p.Val146Ile Uncertain significance ★★ same condition
RBM8A c.343-17C>T Likely benign ★★ same condition
RBM8A c.479+15G>A Benign ★★ same condition
RBM8A p.Gly141= Likely benign ★★ same condition
RBM8A c.*6C>T Pathogenic ★ same condition
RBM8A c.343-6C>G Conflicting classifications of pathogenicity ★ same condition
RBM8A c.-19G>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/rbm8a-p-pro169 (accessed [today's date]).

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