Is RPL17 p.Asn64Ser (c.191A>G) pathogenic?

RPL17 p.Asn64Ser (c.191A>G) is classified Uncertain significance in RPL17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely benign (0.0773); Ultra-rare (popmax 0.0188%, mid).

How common is RPL17 p.Asn64Ser (c.191A>G) in the general population?

RPL17 p.Asn64Ser (c.191A>G) is ultra-rare (popmax 0.0188%, mid) (gnomAD).

What do computational predictors say about RPL17 p.Asn64Ser (c.191A>G)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

RPL17 p.Asn64Ser

c.191A>G · rs376740476 · VCV2277746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -11.02	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,057 bp · p 0.00044 · regional, not allelic
Overall
CADD	24.0	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 0.0188% Middle Eastern · 1/5,318 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00211% 34/1,612,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0188%	5,318
Remaining individualsnot grpmax-eligible	0.00641%	15,593
East Asian	0.00445%	22,450
African / African-American	0.00401%	24,967
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	29,997
South Asian	0.0033%	30,343
European (non-Finnish)	0.00153%	65,549

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.Asn64Ser
Coding: c.191A>G
MANE Select: NM_001035006
dbSNP: rs376740476
Type: single nucleotide variant
Location: chr18:49490818 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.85 · 184 PDB

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.Arg42Gln Uncertain significance ★ ⚠ same type
RPL17 p.Arg62Gly 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-asn64ser (accessed [today's date]).

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