Is RS1 p.Trp147Arg (c.439T>C) pathogenic?

RS1 p.Trp147Arg (c.439T>C) is classified Uncertain significance in RS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-15). AlphaMissense: likely pathogenic (0.9972); Absent from gnomAD v4.1; Associated with X-linked retinoschisis.

What condition is associated with RS1 p.Trp147Arg (c.439T>C)?

RS1 p.Trp147Arg (c.439T>C) is associated with X-linked retinoschisis (ClinVar).

How common is RS1 p.Trp147Arg (c.439T>C) in the general population?

RS1 p.Trp147Arg (c.439T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RS1 p.Trp147Arg (c.439T>C)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

RS1 p.Trp147Arg

c.439T>C · rs2147191229 · VCV1338796

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked retinoschisis

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -12.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.0049 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Trp147Arg
Coding: c.439T>C
MANE Select: NM_001323289 · reported on NM_000330
dbSNP: rs2147191229
Type: single nucleotide variant
Location: chrX:18644513 (GRCh38)

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

Disease context

X-linked retinoschisis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-trp147arg (accessed [today's date]).

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