Is RBBP5 p.Asp381Glu (c.1143C>G) pathogenic?

RBBP5 p.Asp381Glu (c.1143C>G) is classified Uncertain significance in RBBP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely benign (0.1605); Ultra-rare (popmax 0.0196%, amr).

How common is RBBP5 p.Asp381Glu (c.1143C>G) in the general population?

RBBP5 p.Asp381Glu (c.1143C>G) is ultra-rare (popmax 0.0196%, amr) (gnomAD).

What do computational predictors say about RBBP5 p.Asp381Glu (c.1143C>G)?

AlphaMissense predicts likely benign (score 0.1605) — an in-silico prediction, not a clinical call.

RBBP5 p.Asp381Glu

c.1143C>G · VCV3943410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1605 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1605	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -1.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.089	GERP -2.1, phastCons 0.069
Regional constraint	o/e 0.37	unconstrained · MANE · 2,214 bp · p 8.8e-09 · regional, not allelic
Overall
CADD	13.53	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 0.0196% Admixed American · 10/51,000 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00809%

Overall 0.000644% 10/1,551,980 alleles · ultra-rare exomes 8/1,399,804 · genomes 2/152,176 · 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: RBBP5
Protein: p.Asp381Glu
Coding: c.1143C>G
MANE Select: NM_005057
Type: single nucleotide variant
Location: chr1:205097349 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.41 · 32 PDB

Full RBBP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RBBP5 p.Pro146= Benign/Likely benign ★★ same type
RBBP5 p.Thr232Ile Pathogenic ★ ⚠ same type
RBBP5 p.Tyr401Ter Pathogenic ★ same type
RBBP5 p.Arg208Trp Uncertain significance ★ ⚠ same type
RBBP5 p.Arg220Gly Uncertain significance ★ ⚠ same type
RBBP5 p.Arg438Gly Uncertain significance ★ ⚠ same type
RBBP5 p.Arg508Gly Uncertain significance ★ ⚠ same type
RBBP5 p.Asn456Ser 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/rbbp5-p-asp381glu (accessed [today's date]).

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