Is RS1 p.Arg102Pro (c.305G>C) pathogenic?

RS1 p.Arg102Pro (c.305G>C) is classified Likely pathogenic in RS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). AlphaMissense: likely pathogenic (0.9926); Very rare (popmax 0.000112%, nfe).

How common is RS1 p.Arg102Pro (c.305G>C) in the general population?

RS1 p.Arg102Pro (c.305G>C) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about RS1 p.Arg102Pro (c.305G>C)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

RS1 p.Arg102Pro

c.305G>C · rs61752068 · VCV2053270

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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
AlphaMissense	0.9926	likely pathogenic ✓ concordant with ClinVar
REVEL	0.982	strongly pathogenic-leaning
SaProt	LLR -15.90	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.0049 · regional, not allelic
Overall
CADD	30.0	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 0.000112% European (non-Finnish) · 1/895,440 alleles

Overall 8.26e-05% 1/1,211,173 alleles · very rare exomes 1/1,098,003 · genomes 0/113,170 · 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.Arg102Pro
Coding: c.305G>C
MANE Select: NM_000330
dbSNP: rs61752068
Type: single nucleotide variant
Location: chrX:18647212 (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-arg102pro (accessed [today's date]).

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