Is RBP3 p.Ser324= (c.972C>T) pathogenic?

RBP3 p.Ser324= (c.972C>T) is classified Likely benign in RBP3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-13). Very rare (popmax 0.00833%, amr).

How common is RBP3 p.Ser324= (c.972C>T) in the general population?

RBP3 p.Ser324= (c.972C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

RBP3 p.Ser324=

c.972C>T · rs552188961 · VCV792869

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.7	GERP -2.9
Overall
CADD	0.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,030 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00608% 98/1,612,582 alleles · very rare exomes 89/1,460,282 · genomes 9/152,300 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,417
Admixed Americangrpmax	0.00833%	12,006
European (non-Finnish)	0.00686%	14,568
South Asian	0.00329%	30,362
African / African-American	0.00267%	37,518
East Asian	0.00223%	44,868

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser324=
Coding: c.972C>T
MANE Select: NM_002900
dbSNP: rs552188961
Type: single nucleotide variant
Location: chr10:47349456 (GRCh38)
Structure: AlphaFold pLDDT 63.40 · 8 PDB
Residue 324: the 'required for interaction with trim28' region; the 'disordered' region

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

Similar variants

RBP3 p.Ser324Ile Uncertain significance ★ ⚠ same residue
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

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-ser324 (accessed [today's date]).

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