Is RBP3 p.Ala549Val (c.1646C>T) pathogenic?

RBP3 p.Ala549Val (c.1646C>T) is classified Uncertain significance in RBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.8297); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with RBP3 p.Ala549Val (c.1646C>T)?

RBP3 p.Ala549Val (c.1646C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RBP3 p.Ala549Val (c.1646C>T) in the general population?

RBP3 p.Ala549Val (c.1646C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about RBP3 p.Ala549Val (c.1646C>T)?

AlphaMissense predicts likely pathogenic (score 0.8297) — an in-silico prediction, not a clinical call.

RBP3 p.Ala549Val

c.1646C>T · rs782601697 · VCV1501434

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8297	likely pathogenic
SaProt	LLR -14.05	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.5, phastCons 1
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000958% 14/1,460,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,498
African / African-American	0.00133%	75,062
European (non-Finnish)	0.000932%	107,274

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.Ala549Val
Coding: c.1646C>T
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs782601697
Type: single nucleotide variant
Location: chr10:47350130 (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.Ala549Thr Uncertain significance ★★ ⚠ same residue
RBP3 p.Ala549= Conflicting classifications of pathogenicity ★ 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.Ala553Thr 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-ala549val (accessed [today's date]).

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