Is RYK p.Pro52Arg (c.155C>G) pathogenic?

RYK p.Pro52Arg (c.155C>G) is classified Uncertain significance in RYK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-17). AlphaMissense: likely benign (0.1019); No allele count reported in gnomAD v4.1 (AN 1,280,030).

How common is RYK p.Pro52Arg (c.155C>G) in the general population?

RYK p.Pro52Arg (c.155C>G) is no allele count reported in gnomAD v4.1 (AN 1,280,030) (gnomAD).

What do computational predictors say about RYK p.Pro52Arg (c.155C>G)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

RYK p.Pro52Arg

c.155C>G · rs2015586190 · VCV2268034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,280,030)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.98, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 73 kb · p 0.0025 · regional, not allelic
Overall
CADD	15.29	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

No allele count reported in gnomAD v4.1 (AN 1,280,030). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RYK
Protein: p.Pro52Arg
Coding: c.155C>G
MANE Select: NM_002958
dbSNP: rs2015586190
Type: single nucleotide variant
Location: chr3:134250500 (GRCh38)
Gene constraint: LOEUF 0.457 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 80.54 · 1 PDB

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

Similar variants

RYK c.233-4C>G Benign ★★ same type
RYK p.Arg51Trp Benign ★★ same type
RYK p.Lys464Arg Benign ★★ same type
RYK c.355-4703C>G Uncertain significance ★ same type
RYK p.Arg424Ter Uncertain significance ★ same type
RYK p.Asp287Glu Uncertain significance ★ ⚠ same type
RYK p.Ile303Val Uncertain significance ★ ⚠ same type
RYK p.Ile325Leu Conflicting classifications of pathogenicity ★ ⚠ 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/ryk-p-pro52arg (accessed [today's date]).

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