Is RPL17 p.Arg42Gln (c.125G>A) pathogenic?

RPL17 p.Arg42Gln (c.125G>A) is classified Uncertain significance in RPL17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: ambiguous (0.4164); Very rare (popmax 8.48e-05%, nfe).

How common is RPL17 p.Arg42Gln (c.125G>A) in the general population?

RPL17 p.Arg42Gln (c.125G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about RPL17 p.Arg42Gln (c.125G>A)?

AlphaMissense predicts ambiguous (score 0.4164) — an in-silico prediction, not a clinical call.

RPL17 p.Arg42Gln

c.125G>A · VCV4156528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4164	ambiguous
REVEL	0.181	moderately benign-leaning
SaProt	LLR -13.56	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.91, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,057 bp · p 0.00044 · regional, not allelic
Overall
CADD	26.9	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 8.48e-05% European (non-Finnish) · 1/1,179,914 alleles

Overall 6.2e-05% 1/1,613,876 alleles · very rare exomes 1/1,461,574 · genomes 0/152,302 · 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: RPL17
Protein: p.Arg42Gln
Coding: c.125G>A
MANE Select: NM_001035006
Type: single nucleotide variant
Location: chr18:49490884 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.85 · 184 PDB
Residue 42: an α-helix

Full RPL17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPL23 p.Arg89Gly Uncertain significance ★★ ⚠ same type
RPL23 p.Arg89His Uncertain significance ★★ ⚠ same type
RPL23 p.Ile132Val Uncertain significance ★★ ⚠ same type
RPL17 p.Arg30His Uncertain significance ★ ⚠ same type
RPL17 p.Arg62Gly Uncertain significance ★ ⚠ same type
RPL17 p.Asn64Ser Uncertain significance ★ ⚠ same type
RPL17 p.Gln56Leu Uncertain significance ★ ⚠ same type
RPL17 p.Glu115Gln 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/rpl17-p-arg42gln (accessed [today's date]).

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