Is RBP3 p.Glu112Asp (c.336A>C) pathogenic?

RBP3 p.Glu112Asp (c.336A>C) is classified Uncertain significance in RBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). AlphaMissense: likely benign (0.1389); Very rare (popmax 0.00585%, nfe).

How common is RBP3 p.Glu112Asp (c.336A>C) in the general population?

RBP3 p.Glu112Asp (c.336A>C) is very rare (popmax 0.00585%, nfe) (gnomAD).

What do computational predictors say about RBP3 p.Glu112Asp (c.336A>C)?

AlphaMissense predicts likely benign (score 0.1389) — an in-silico prediction, not a clinical call.

RBP3 p.Glu112Asp

c.336A>C · rs782635160 · VCV854333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1389 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1389	likely benign
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2.8
Overall
CADD	16.42	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00585% European (non-Finnish) · 69/1,180,028 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.0044% 71/1,613,696 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00585%	17,102
African / African-American	0.00267%	37,461

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.Glu112Asp
Coding: c.336A>C
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782635160
Type: single nucleotide variant
Location: chr10:47348820 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 112: 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

Similar variants

RBP3 p.Arg388Ter Pathogenic ★★ same type
RBP3 p.Gln141Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Gln54Ter Pathogenic ★★ same type
RBP3 p.Glu149Ter Pathogenic ★★ same type
RBP3 p.Glu692Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Tyr784Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 p.Tyr841Ter Pathogenic/Likely pathogenic ★★ same type
RBP3 c.3388+4C>G 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/rbp3-p-glu112asp (accessed [today's date]).

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