Is RPL17 p.Thr52Ala (c.154A>G) pathogenic?

RPL17 p.Thr52Ala (c.154A>G) is classified Uncertain significance in RPL17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.141); Very rare (popmax 0.000254%, nfe).

How common is RPL17 p.Thr52Ala (c.154A>G) in the general population?

RPL17 p.Thr52Ala (c.154A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about RPL17 p.Thr52Ala (c.154A>G)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

RPL17 p.Thr52Ala

c.154A>G · VCV4156526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -12.77	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,057 bp · p 0.00044 · regional, not allelic
Overall
CADD	24.8	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 0.000254% European (non-Finnish) · 3/1,179,908 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,528 alleles · very rare exomes 3/1,461,192 · genomes 0/152,336 · 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.Thr52Ala
Coding: c.154A>G
MANE Select: NM_001035006
Type: single nucleotide variant
Location: chr18:49490855 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.85 · 184 PDB
Residue 52: 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.Arg42Gln 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

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-thr52ala (accessed [today's date]).

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