Is RNPC3 p.His348Arg (c.1043A>G) pathogenic?

RNPC3 p.His348Arg (c.1043A>G) is classified Uncertain significance in RNPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.0564); Very rare (popmax 0.00141%, afr); Associated with Inborn genetic diseases.

What condition is associated with RNPC3 p.His348Arg (c.1043A>G)?

RNPC3 p.His348Arg (c.1043A>G) is associated with Inborn genetic diseases (ClinVar).

How common is RNPC3 p.His348Arg (c.1043A>G) in the general population?

RNPC3 p.His348Arg (c.1043A>G) is very rare (popmax 0.00141%, afr) (gnomAD).

What do computational predictors say about RNPC3 p.His348Arg (c.1043A>G)?

AlphaMissense predicts likely benign (score 0.0564) — an in-silico prediction, not a clinical call.

RNPC3 p.His348Arg

c.1043A>G · rs1276427947 · VCV2273386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0564 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00141%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0564	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.17	GERP -3.1, phastCons 0.002
Regional constraint	o/e 1.07	unconstrained · MANE · 20 kb · p 0.11 · regional, not allelic
Overall
CADD	3.284	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 0.00141% African / African-American · 1/70,842 alleles

Overall 6.67e-05% 1/1,499,458 alleles · very rare exomes 0/1,347,636 · genomes 1/151,822 · joint denominator

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: RNPC3
Protein: p.His348Arg
Coding: c.1043A>G
MANE Select: NM_017619
dbSNP: rs1276427947
Type: single nucleotide variant
Location: chr1:103543445 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.73 · 2 PDB
Residue 348: the 'necessary for binding to m(7)g-capped u12 snrna' region

Full RNPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RNPC3 p.Ala204Val Uncertain significance ★ ⚠ same condition
RNPC3 p.Arg120Gly Uncertain significance ★ ⚠ same condition
RNPC3 p.Arg205Gln Uncertain significance ★ ⚠ same condition
RNPC3 p.Arg254Gln Uncertain significance ★ ⚠ same condition
RNPC3 p.Arg277Cys Uncertain significance ★ ⚠ same condition
RNPC3 p.Arg452Trp Uncertain significance ★ ⚠ same condition
RNPC3 p.Arg458Leu Uncertain significance ★ ⚠ same condition
RNPC3 p.Arg464His 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/rnpc3-p-his348arg (accessed [today's date]).

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