Is RS1 p.Arg174= (c.522G>A) pathogenic?

RS1 p.Arg174= (c.522G>A) is classified Likely benign in RS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). Ultra-rare (popmax 0.0546%, sas).

How common is RS1 p.Arg174= (c.522G>A) in the general population?

RS1 p.Arg174= (c.522G>A) is ultra-rare (popmax 0.0546%, sas) (gnomAD).

RS1 p.Arg174=

c.522G>A · rs762407219 · VCV1097162

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, sas)

⚠ 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 2.7	GERP 2, phastCons 1
Overall
CADD	18.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0546% South Asian · 31/56,747 alleles

Filtering AF 0.0395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0343%

Overall 0.00265% 32/1,208,947 alleles · ultra-rare exomes 31/1,097,815 · genomes 1/111,132 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0546%	1,831
Middle Eastern	0.0229%	4,361

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.Arg174=
Coding: c.522G>A
MANE Select: NM_000330
dbSNP: rs762407219
Type: single nucleotide variant
Location: chrX:18644430 (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-arg174 (accessed [today's date]).

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