Is USH2A p.Ser5030= (c.15090G>A) pathogenic?

USH2A p.Ser5030= (c.15090G>A) is classified Likely benign in USH2A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-05). Ultra-rare (popmax 0.08%, amr); Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Ser5030= (c.15090G>A)?

USH2A p.Ser5030= (c.15090G>A) is associated with retinitis pigmentosa 39, Usher syndrome type 2A (ClinVar).

How common is USH2A p.Ser5030= (c.15090G>A) in the general population?

USH2A p.Ser5030= (c.15090G>A) is ultra-rare (popmax 0.08%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

USH2A p.Ser5030=

c.15090G>A · rs397517997 · VCV48454

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.08%, amr)

Conditions

retinitis pigmentosa 39

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.9
Overall
CADD	0.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.08% Admixed American · 48/60,024 alleles

Filtering AF 0.0619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0555%

Overall 0.00675% 109/1,614,230 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.08%	1,251
Remaining individualsnot grpmax-eligible	0.0176%	5,683
African / African-American	0.00799%	12,510
East Asian	0.00668%	14,962
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.00329%	30,361
European (non-Finnish)	0.00314%	31,893

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: USH2A
Protein: p.Ser5030=
Coding: c.15090G>A
MANE Select: NM_206933
dbSNP: rs397517997
Type: single nucleotide variant
Location: chr1:215634666 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

Full USH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 39 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 2A

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

USH2A p.Ser5030Ter Pathogenic ★★ same residue
USH2A p.Ser5030Leu Uncertain significance ★ ⚠ same residue
USH2A c.12295-3T>A Pathogenic ★★★ same condition
USH2A c.8559-2A>G Pathogenic ★★★ same condition
USH2A c.8682-9A>G Pathogenic ★★★ same condition
USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same condition
USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same condition
USH2A p.Arg4192Cys Likely pathogenic ★★★ ⚠ same condition

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/ush2a-p-ser5030 (accessed [today's date]).

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