Is RS1 p.Ser180Pro (c.538T>C) pathogenic?

RS1 p.Ser180Pro (c.538T>C) is classified Pathogenic in RS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-01-01). AlphaMissense: likely pathogenic (0.8897); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with RS1 p.Ser180Pro (c.538T>C)?

RS1 p.Ser180Pro (c.538T>C) is associated with inherited retinal dystrophy (ClinVar).

How common is RS1 p.Ser180Pro (c.538T>C) in the general population?

RS1 p.Ser180Pro (c.538T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RS1 p.Ser180Pro (c.538T>C)?

AlphaMissense predicts likely pathogenic (score 0.8897) — an in-silico prediction, not a clinical call.

RS1 p.Ser180Pro

c.538T>C · VCV3249916

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.8897	likely pathogenic ✓ concordant with ClinVar
REVEL	0.843	moderately pathogenic-leaning
SaProt	LLR -11.30	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 1.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.0049 · regional, not allelic
Overall
CADD	26.1	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.Ser180Pro
Coding: c.538T>C
MANE Select: NM_001323289 · reported on NM_000330
Type: single nucleotide variant
Location: chrX:18642141 (GRCh38)

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

Disease context

inherited retinal dystrophy — 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-ser180pro (accessed [today's date]).

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