Is USH2A p.Ser2773= (c.8319C>T) pathogenic?

USH2A p.Ser2773= (c.8319C>T) is classified Benign/Likely benign in USH2A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.17%, afr); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Ser2773= (c.8319C>T)?

USH2A p.Ser2773= (c.8319C>T) is associated with Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Ser2773= (c.8319C>T) in the general population?

USH2A p.Ser2773= (c.8319C>T) is low-frequency (popmax 1.17%, afr) (gnomAD).

USH2A p.Ser2773=

c.8319C>T · rs56829872 · VCV178646

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.17%, afr)

Conditions

Usher syndrome type 2A

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 -0.01	GERP -2.2
Overall
CADD	3.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.17% African / African-American · 880/75,012 alleles

Filtering AF 1.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.0644% 1,039/1,613,946 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.17%	85
Admixed American	0.137%	732
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,357
East Asian	0.00223%	44,874
European (non-Finnish)	0.0017%	58,994

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.Ser2773=
Coding: c.8319C>T
MANE Select: NM_206933
dbSNP: rs56829872
Type: single nucleotide variant
Location: chr1:215879003 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2773: the fibronectin type-iii 14 domain

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

Disease context

Usher syndrome type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 39

Similar variants

USH2A p.Ser2773Phe Uncertain significance ★★ ⚠ same residue
USH2A p.Ser2773Cys 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-ser2773 (accessed [today's date]).

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