Is RBP3 p.Arg122Cys (c.364C>T) pathogenic?

RBP3 p.Arg122Cys (c.364C>T) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1025); Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with RBP3 p.Arg122Cys (c.364C>T)?

RBP3 p.Arg122Cys (c.364C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RBP3 p.Arg122Cys (c.364C>T) in the general population?

RBP3 p.Arg122Cys (c.364C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about RBP3 p.Arg122Cys (c.364C>T)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

RBP3 p.Arg122Cys

c.364C>T · VCV4151962

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
SaProt	LLR -11.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.56, phastCons 0.035
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00235% 38/1,613,898 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
African / African-American	0.004%	25,019
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
South Asian	0.00329%	30,362
European (non-Finnish)	0.0022%	45,386
Remaining individualsnot grpmax-eligible	0.0016%	62,506
Finnishnot grpmax-eligible	0.00157%	63,738

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: RBP3
Protein: p.Arg122Cys
Coding: c.364C>T
MANE Select: NM_005225 · reported on NM_002900
Type: single nucleotide variant
Location: chr10:47348848 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 122: a DNA-binding region; the 'interaction with birc2/c-iap1' region; the 'disordered' region

Full RBP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RBP3 p.Arg122His Uncertain significance ⚠ same residue
RBP3 p.Ala1224Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala243Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala252Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala420Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala424Val Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala549Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala549Val 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/rbp3-p-arg122cys (accessed [today's date]).

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