Is RRP1B p.Arg306Gln (c.917G>A) pathogenic?

RRP1B p.Arg306Gln (c.917G>A) is classified Uncertain significance in RRP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely benign (0.1151); Ultra-rare (popmax 0.01%, amr).

How common is RRP1B p.Arg306Gln (c.917G>A) in the general population?

RRP1B p.Arg306Gln (c.917G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about RRP1B p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.1151) — an in-silico prediction, not a clinical call.

RRP1B p.Arg306Gln

c.917G>A · VCV3435641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1151 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1151	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 34 kb · p 1.5e-05 · regional, not allelic
Overall
CADD	26.3	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 0.01% Admixed American · 6/59,980 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00149% 24/1,613,886 alleles · ultra-rare exomes 17/1,461,860 · genomes 7/152,026 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,997
South Asian	0.00549%	18,214
African / African-American	0.00534%	18,718
Remaining individualsnot grpmax-eligible	0.0048%	20,826
Finnishnot grpmax-eligible	0.00156%	64,012
European (non-Finnish)	0.000424%	236,000

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: RRP1B
Protein: p.Arg306Gln
Coding: c.917G>A
MANE Select: NM_015056
Type: single nucleotide variant
Location: chr21:43684578 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.63 · 2 PDB

Full RRP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RRP1B p.Thr708Met Uncertain significance ★★ ⚠ same type
RRP1B p.Leu631Pro Benign ★★ same type
RRP1B p.Val82= Benign ★★ same type
RRP1B p.Ala346Val Uncertain significance ★ ⚠ same type
RRP1B p.Ala490Val Uncertain significance ★ ⚠ same type
RRP1B p.Ala575Val Uncertain significance ★ ⚠ same type
RRP1B p.Ala671Asp Uncertain significance ★ ⚠ same type
RRP1B p.Ala671Ser Uncertain significance ★ ⚠ 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/rrp1b-p-arg306gln (accessed [today's date]).

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