Is RRBP1 p.Ser32Phe (c.95C>T) pathogenic?

RRBP1 p.Ser32Phe (c.95C>T) is classified Uncertain significance in RRBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely pathogenic (0.9111); Ultra-rare (popmax 0.045%, amr).

How common is RRBP1 p.Ser32Phe (c.95C>T) in the general population?

RRBP1 p.Ser32Phe (c.95C>T) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about RRBP1 p.Ser32Phe (c.95C>T)?

AlphaMissense predicts likely pathogenic (score 0.9111) — an in-silico prediction, not a clinical call.

RRBP1 p.Ser32Phe

c.95C>T · VCV3435503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9111	likely pathogenic · top 3% in RRBP1
REVEL	0.427	indeterminate
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 935 bp · p 0.63 · regional, not allelic
Overall
CADD	32.0	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 0.045% Admixed American · 27/59,974 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00217% 35/1,613,926 alleles · ultra-rare exomes 16/1,461,876 · genomes 19/152,050 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,221
Remaining individualsnot grpmax-eligible	0.0096%	10,413
African / African-American	0.00134%	74,858
European (non-Finnish)	8.47e-05%	1,180,026

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: RRBP1
Protein: p.Ser32Phe
Coding: c.95C>T
MANE Select: NM_001365613
Type: single nucleotide variant
Location: chr20:17660413 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.52

Full RRBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RRBP1 p.Ala1366Thr Uncertain significance ★★ ⚠ same type
RRBP1 c.3867+8C>T Benign ★★ same type
RRBP1 p.Arg1369Lys Benign ★★ same type
RRBP1 p.His1099Tyr Benign ★★ same type
RRBP1 p.Leu1177= Benign/Likely benign ★★ same type
RRBP1 p.Pro639Ser Likely benign ★★ same type
RRBP1 p.Ser997= Benign ★★ same type
RRBP1 p.Thr1138= Benign ★★ 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/rrbp1-p-ser32phe (accessed [today's date]).

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