Is USH2A p.Pro3671= (c.11013T>G) pathogenic?

USH2A p.Pro3671= (c.11013T>G) is classified Likely benign in USH2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.0156%, nfe).

How common is USH2A p.Pro3671= (c.11013T>G) in the general population?

USH2A p.Pro3671= (c.11013T>G) is ultra-rare (popmax 0.0156%, nfe) (gnomAD).

USH2A p.Pro3671=

c.11013T>G · rs777699434 · VCV444197

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, 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 4.5	GERP 1.9, phastCons 1
Overall
CADD	9.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% European (non-Finnish) · 184/1,179,662 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.012% 194/1,613,568 alleles · ultra-rare exomes 182/1,461,444 · genomes 12/152,124 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0156%	6,411
Remaining individualsnot grpmax-eligible	0.008%	12,495
African / African-American	0.00668%	14,979

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.Pro3671=
Coding: c.11013T>G
MANE Select: NM_206933
dbSNP: rs777699434
Type: single nucleotide variant
Location: chr1:215766715 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3671: the fibronectin type-iii 21 domain

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

Similar variants

USH2A p.Pro3671Ala Uncertain significance ★ ⚠ same residue
USH2A p.Pro3671Leu Uncertain significance ★ same residue
USH2A p.Pro3671fs 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-pro3671 (accessed [today's date]).

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