Is USH2A p.Asp510= (c.1530C>T) pathogenic?

USH2A p.Asp510= (c.1530C>T) is classified Conflicting classifications of pathogenicity in USH2A (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-28). Rare (popmax 0.775%, sas); Associated with retinitis pigmentosa.

What condition is associated with USH2A p.Asp510= (c.1530C>T)?

USH2A p.Asp510= (c.1530C>T) is associated with retinitis pigmentosa, Usher syndrome type 2A (ClinVar).

How common is USH2A p.Asp510= (c.1530C>T) in the general population?

USH2A p.Asp510= (c.1530C>T) is rare (popmax 0.775%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

USH2A p.Asp510=

c.1530C>T · rs200940197 · VCV178992

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.775%, sas)

Conditions

retinitis pigmentosa

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 -2.1	GERP -3.6
Overall
CADD	1.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.775% South Asian · 706/91,064 alleles

Filtering AF 0.728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.709%

Overall 0.0491% 792/1,613,196 alleles · rare exomes 744/1,461,292 · genomes 48/151,904 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.775%	129
Remaining individualsnot grpmax-eligible	0.0736%	1,358
Middle Eastern	0.0165%	6,052
East Asian	0.0112%	8,956
Admixed American	0.00835%	11,983
African / African-American	0.004%	24,971
European (non-Finnish)	0.0022%	45,369

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.Asp510=
Coding: c.1530C>T
MANE Select: NM_206933
dbSNP: rs200940197
Type: single nucleotide variant
Location: chr1:216323494 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 510: the laminin n-terminal domain

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

Disease context

retinitis pigmentosa — 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 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
USH2A p.Asn346His Pathogenic ★★★ same condition
USH2A p.Asn4292Asp 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-asp510 (accessed [today's date]).

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