Is RS1 p.Pro192= (c.576C>A) pathogenic?

RS1 p.Pro192= (c.576C>A) is classified Likely benign in RS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-18). Very rare (popmax 0.00296%, eas).

How common is RS1 p.Pro192= (c.576C>A) in the general population?

RS1 p.Pro192= (c.576C>A) is very rare (popmax 0.00296%, eas) (gnomAD).

RS1 p.Pro192=

c.576C>A · rs186334493 · VCV1140455

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.16	GERP -3.3, phastCons 0.86
Overall
CADD	6.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,822 alleles

Overall 8.25e-05% 1/1,211,640 alleles · very rare exomes 1/1,098,005 · genomes 0/113,635 · 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: RS1
Protein: p.Pro192=
Coding: c.576C>A
MANE Select: NM_000330
dbSNP: rs186334493
Type: single nucleotide variant
Location: chrX:18642103 (GRCh38)

Full RS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/rs1-p-pro192 (accessed [today's date]).

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