Is USH2A p.Pro560fs (c.1679del) pathogenic?

USH2A p.Pro560fs (c.1679del) is classified Pathogenic in USH2A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2025-11-11). Very rare (popmax 0.0067%, nfe); Associated with USH2A-related disorder.

What condition is associated with USH2A p.Pro560fs (c.1679del)?

USH2A p.Pro560fs (c.1679del) is associated with USH2A-related disorder, Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Pro560fs (c.1679del) in the general population?

USH2A p.Pro560fs (c.1679del) is very rare (popmax 0.0067%, nfe) (gnomAD).

USH2A p.Pro560fs

c.1679del · rs773539640 · VCV286104

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0067%, nfe)

Conditions

USH2A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.69	GERP -2.7, phastCons 0.96
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% European (non-Finnish) · 79/1,179,952 alleles

Filtering AF 0.00546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00508% 82/1,613,932 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0067%	14,936
African / African-American	0.00267%	37,464
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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.Pro560fs
Coding: c.1679del
MANE Select: NM_206933
dbSNP: rs773539640
Type: Deletion
Location: chr1:216292336 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 560: a disulfide bond; the laminin egf-like 1 domain

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

Disease context

Also linked: Usher syndrome type 2A retinitis pigmentosa 39 Usher syndrome

Similar variants

USH2A p.Pro560Ala Conflicting classifications of pathogenicity ★ same residue
USH2A c.12295-?_14133+?del Likely pathogenic ★★★ same condition
USH2A c.11389+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.11549del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.4251+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.4758+1del Pathogenic/Likely pathogenic ★★ same condition
USH2A c.486-4_486-2del Likely pathogenic ★★ same condition
USH2A c.7594+2del 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-pro560fs (accessed [today's date]).

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