Is RRP12 p.Phe809= (c.2427C>T) pathogenic?

RRP12 p.Phe809= (c.2427C>T) is classified Benign in RRP12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-06-07). Common (popmax 7.94%, afr) — too common for a highly-penetrant pathogenic allele.

RRP12 p.Phe809=

Q: How common is RRP12 p.Phe809= (c.2427C>T) in the general population?

RRP12 p.Phe809= (c.2427C>T) is common (popmax 7.94%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2427C>T · rs61739160 · VCV776533

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.94%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -3.9	GERP -4.4
Overall
CADD	16.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.94% African / African-American · 5,955/74,992 alleles

Filtering AF 7.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.7%

Overall 0.467% 7,531/1,613,926 alleles · common exomes 4,041/1,461,748 · genomes 3,490/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.94%	13
Admixed American	0.73%	137
Remaining individualsnot grpmax-eligible	0.654%	153
Amishnot grpmax-eligible	0.549%	182
Middle Eastern	0.495%	202
Ashkenazi Jewishnot grpmax-eligible	0.186%	538
European (non-Finnish)	0.0522%	1,916
South Asian	0.022%	4,554
Finnishnot grpmax-eligible	0.00313%	31,981
East Asian	0.00223%	44,864

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: RRP12
Protein: p.Phe809=
Coding: c.2427C>T
MANE Select: NM_015179
dbSNP: rs61739160
Type: single nucleotide variant
Location: chr10:97370998 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 8 PDB
Residue 809: an α-helix

Full RRP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RRP12 p.Ser745Gly Likely benign ★★ same type
RRP12 p.Ala1066Thr Uncertain significance ★ ⚠ same type
RRP12 p.Ala1150Thr Uncertain significance ★ ⚠ same type
RRP12 p.Ala120Val Uncertain significance ★ ⚠ same type
RRP12 p.Ala1227Val Uncertain significance ★ ⚠ same type
RRP12 p.Ala149Thr Uncertain significance ★ ⚠ same type
RRP12 p.Ala193Pro Uncertain significance ★ ⚠ same type
RRP12 p.Ala193Val 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/rrp12-p-phe809 (accessed [today's date]).

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