Is USH2A p.Thr2016= (c.6048A>G) pathogenic?

USH2A p.Thr2016= (c.6048A>G) is classified Uncertain significance in USH2A (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-23). Very rare (popmax 0.00133%, afr); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Thr2016= (c.6048A>G)?

USH2A p.Thr2016= (c.6048A>G) is associated with Usher syndrome type 2A (ClinVar).

How common is USH2A p.Thr2016= (c.6048A>G) in the general population?

USH2A p.Thr2016= (c.6048A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

USH2A p.Thr2016=

c.6048A>G · rs995870865 · VCV834823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.9	GERP -0.54, phastCons 1
Overall
CADD	10.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,938 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,838 alleles · very rare exomes 4/1,461,610 · genomes 2/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,938
European (non-Finnish)	0.000424%	235,977

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.Thr2016=
Coding: c.6048A>G
MANE Select: NM_206933
dbSNP: rs995870865
Type: single nucleotide variant
Location: chr1:216070102 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2016: the fibronectin type-iii 6 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

Similar variants

USH2A p.Thr2016Lys Uncertain significance ★★ same residue
USH2A p.Thr2016Ile 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-thr2016 (accessed [today's date]).

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