Is RS1 p.Ser95= (c.285G>A) pathogenic?

RS1 p.Ser95= (c.285G>A) is classified Benign/Likely benign in RS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0623%, eas); Associated with X-linked retinoschisis.

What condition is associated with RS1 p.Ser95= (c.285G>A)?

RS1 p.Ser95= (c.285G>A) is associated with X-linked retinoschisis (ClinVar).

How common is RS1 p.Ser95= (c.285G>A) in the general population?

RS1 p.Ser95= (c.285G>A) is ultra-rare (popmax 0.0623%, eas) (gnomAD).

RS1 p.Ser95=

c.285G>A · rs143920122 · VCV738705

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0623%, eas)

Conditions

X-linked retinoschisis

⚠ 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
Constraint at this position
Conservation	phyloP -6.4	GERP -3.7
Overall
CADD	0.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0623% East Asian · 21/33,715 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.0108% 131/1,208,677 alleles · ultra-rare exomes 111/1,097,880 · genomes 20/110,797 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.268%	373
East Asiangrpmax	0.0623%	1,605
Remaining individualsnot grpmax-eligible	0.021%	4,756
African / African-American	0.00704%	14,207
Admixed American	0.00439%	22,787
European (non-Finnish)	0.0038%	26,321
South Asian	0.00176%	56,706

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser95=
Coding: c.285G>A
MANE Select: NM_000330
dbSNP: rs143920122
Type: single nucleotide variant
Location: chrX:18647232 (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-ser95 (accessed [today's date]).

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