Is USH2A p.Cys577= (c.1731C>T) pathogenic?

USH2A p.Cys577= (c.1731C>T) is classified Benign/Likely benign in USH2A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.54%, sas); Associated with retinitis pigmentosa.

What condition is associated with USH2A p.Cys577= (c.1731C>T)?

USH2A p.Cys577= (c.1731C>T) is associated with retinitis pigmentosa, Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Cys577= (c.1731C>T) in the general population?

USH2A p.Cys577= (c.1731C>T) is low-frequency (popmax 3.54%, 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.Cys577=

c.1731C>T · rs41313732 · VCV48474

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.54%, 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 3.8	GERP -0.35, phastCons 1
Overall
CADD	9.639	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.54% South Asian · 3,221/91,078 alleles

Filtering AF 3.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.39%

Overall 0.214% 3,460/1,614,086 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.54%	28
Remaining individualsnot grpmax-eligible	0.28%	357
Middle Eastern	0.264%	379
African / African-American	0.00799%	12,508
European (non-Finnish)	0.00339%	29,499
Admixed American	0.00333%	30,011

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.Cys577=
Coding: c.1731C>T
MANE Select: NM_206933
dbSNP: rs41313732
Type: single nucleotide variant
Location: chr1:216292284 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 577: a disulfide bond; the laminin egf-like 2 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 retinitis pigmentosa 39

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.Cys577Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
USH2A p.Cys577Tyr Likely pathogenic ★ 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-cys577 (accessed [today's date]).

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