Is RBP3 p.Ser163Pro (c.487T>C) pathogenic?

RBP3 p.Ser163Pro (c.487T>C) is classified Benign in RBP3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.3147); Low-frequency (popmax 2.04%, afr); Associated with retinitis pigmentosa.

What condition is associated with RBP3 p.Ser163Pro (c.487T>C)?

RBP3 p.Ser163Pro (c.487T>C) is associated with retinitis pigmentosa, retinitis pigmentosa 66 (ClinVar).

How common is RBP3 p.Ser163Pro (c.487T>C) in the general population?

RBP3 p.Ser163Pro (c.487T>C) is low-frequency (popmax 2.04%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RBP3 p.Ser163Pro (c.487T>C)?

AlphaMissense predicts likely benign (score 0.3147) — an in-silico prediction, not a clinical call.

RBP3 p.Ser163Pro

c.487T>C · rs35686775 · VCV208295

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.3147 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.04%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.3147	likely benign
SaProt	LLR -11.41	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 5.5	GERP 0.54, phastCons 1
Overall
CADD	22.8	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 2.04% African / African-American · 1,530/75,038 alleles

Filtering AF 1.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.92%

Overall 0.104% 1,682/1,613,894 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.04%	49
Remaining individualsnot grpmax-eligible	0.115%	868
Admixed American	0.112%	896
Middle Eastern	0.033%	3,031
South Asian	0.00439%	22,768
European (non-Finnish)	0.000593%	168,572

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.Ser163Pro
Coding: c.487T>C
MANE Select: NM_005225 · reported on NM_002900
dbSNP: rs35686775
Type: single nucleotide variant
Location: chr10:47348971 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 163: a DNA-binding region; the 'interaction with birc2/c-iap1' region; the 'leucine-zipper' region

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 66

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

RBP3 p.Ser163= Likely benign ★ same residue
RBP3 p.Arg388Ter Pathogenic ★★ same condition
RBP3 p.Gln54Ter Pathogenic ★★ same condition
RBP3 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala312Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala325Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala379Thr Uncertain significance ★★ ⚠ same condition
RBP3 p.Ala403Thr 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-ser163pro (accessed [today's date]).

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