Is RS1 p.Ser84Cys (c.251C>G) pathogenic?

RS1 p.Ser84Cys (c.251C>G) is classified Conflicting classifications of pathogenicity in RS1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.6987); Absent from gnomAD v4.1.

How common is RS1 p.Ser84Cys (c.251C>G) in the general population?

RS1 p.Ser84Cys (c.251C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RS1 p.Ser84Cys (c.251C>G)?

AlphaMissense predicts likely pathogenic (score 0.6987) — an in-silico prediction, not a clinical call.

RS1 p.Ser84Cys

c.251C>G · rs1338396929 · VCV2901748

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6987	likely pathogenic
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -12.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.0049 · regional, not allelic
Overall
CADD	27.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RS1
Protein: p.Ser84Cys
Coding: c.251C>G
MANE Select: NM_001323289 · reported on NM_000330
dbSNP: rs1338396929
Type: single nucleotide variant
Location: chrX:18647266 (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-ser84cys (accessed [today's date]).

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