Is USH2A p.Pro4601= (c.13803A>T) pathogenic?

USH2A p.Pro4601= (c.13803A>T) is classified Likely benign in USH2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-18). Very rare (popmax 8.47e-05%, nfe).

How common is USH2A p.Pro4601= (c.13803A>T) in the general population?

USH2A p.Pro4601= (c.13803A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

USH2A p.Pro4601=

c.13803A>T · rs929186272 · VCV866445

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 -3.6
Overall
CADD	0.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,978 alleles

Overall 6.2e-05% 1/1,614,064 alleles · very rare exomes 1/1,461,798 · genomes 0/152,266 · joint denominator

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.Pro4601=
Coding: c.13803A>T
MANE Select: NM_206933
dbSNP: rs929186272
Type: single nucleotide variant
Location: chr1:215674108 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4601: the fibronectin type-iii 31 domain

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

Similar variants

USH2A p.Pro4601Leu Uncertain significance ★★ ⚠ same residue
USH2A p.Pro4601Ala Uncertain significance same residue
USH2A p.Pro4601fs Pathogenic ★ same residue
USH2A c.12295-3T>A Pathogenic ★★★ same type
USH2A c.8559-2A>G Pathogenic ★★★ same type
USH2A c.8682-9A>G Pathogenic ★★★ same type
USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same type
USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same type

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-pro4601 (accessed [today's date]).

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