Is RBP3 p.Met859Val (c.2575A>G) pathogenic?

RBP3 p.Met859Val (c.2575A>G) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-10). AlphaMissense: likely benign (0.1961); Very rare (popmax 0.0089%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RBP3 p.Met859Val (c.2575A>G)?

RBP3 p.Met859Val (c.2575A>G) is associated with Inborn genetic diseases (ClinVar).

How common is RBP3 p.Met859Val (c.2575A>G) in the general population?

RBP3 p.Met859Val (c.2575A>G) is very rare (popmax 0.0089%, nfe) (gnomAD).

What do computational predictors say about RBP3 p.Met859Val (c.2575A>G)?

AlphaMissense predicts likely benign (score 0.1961) — an in-silico prediction, not a clinical call.

RBP3 p.Met859Val

c.2575A>G · rs577807789 · VCV935582

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0089%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1961	likely benign
SaProt	LLR -9.25	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 8.6	GERP 0.35, phastCons 1
Overall
CADD	21.2	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 0.0089% European (non-Finnish) · 105/1,179,866 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00683% 110/1,611,438 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0089%	11,237
Remaining individualsnot grpmax-eligible	0.00801%	12,490

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.Met859Val
Coding: c.2575A>G
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs577807789
Type: single nucleotide variant
Location: chr10:47351059 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB

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.Met859Arg Uncertain significance ★ ⚠ same residue
RBP3 p.Met859Thr 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

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-met859val (accessed [today's date]).

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