Is RS1 p.Ile136= (c.408C>T) pathogenic?

RS1 p.Ile136= (c.408C>T) is classified Likely benign in RS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-24). Absent from gnomAD v4.1.

How common is RS1 p.Ile136= (c.408C>T) in the general population?

RS1 p.Ile136= (c.408C>T) is absent from gnomAD v4.1 (gnomAD).

RS1 p.Ile136=

c.408C>T · rs2518919854 · VCV2057414

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

⚠ 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
Pangolin	Δ0.27	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 4.5	GERP 1, phastCons 1
Overall
CADD	16.93	PHRED · no single calibrated threshold — expert panels disagree

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.Ile136=
Coding: c.408C>T
MANE Select: NM_000330
dbSNP: rs2518919854
Type: single nucleotide variant
Location: chrX:18644544 (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-ile136 (accessed [today's date]).

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