Is USH2A p.Ser2389= (c.7167C>T) pathogenic?

USH2A p.Ser2389= (c.7167C>T) is classified Likely benign in USH2A (ClinVar, Expert panel, 5 submitters; last evaluated 2020-05-26). Rare (popmax 0.176%, eas); Associated with Usher syndrome.

What condition is associated with USH2A p.Ser2389= (c.7167C>T)?

USH2A p.Ser2389= (c.7167C>T) is associated with Usher syndrome, Usher syndrome type 2A (ClinVar).

How common is USH2A p.Ser2389= (c.7167C>T) in the general population?

USH2A p.Ser2389= (c.7167C>T) is rare (popmax 0.176%, eas) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

USH2A p.Ser2389=

c.7167C>T · rs200243588 · VCV681822

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.176%, eas)

Conditions

Usher syndrome

ClinGen expert panel — Hearing Loss VCEP

Likely Benign for Usher syndrome. Applied ACMG criteria (verbatim):

BP7 BP4 BS1_Supporting

Curation rationale (ClinGen, verbatim)

The filtering allele frequency (the lower threshold of the 95% CI of 57/19928 of the c.7167C>T (p.Ser2389=) variant in the USH2A gene is 0.22% for East Asian chromosomes by gnomAD v2.1.1, which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). The silent c.7167C>T variant in USH2A is not predicted by the computational prediction analysis using MaxEntScan to impact splicing (BP4, BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1_P, BP4,BP7.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 -1	GERP -4.8
Overall
CADD	1.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.176% East Asian · 79/44,818 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.133%

Overall 0.00998% 161/1,612,596 alleles · rare exomes 141/1,460,608 · genomes 20/151,988 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.176%	567
South Asian	0.0494%	2,024
Remaining individualsnot grpmax-eligible	0.0208%	4,802
European (non-Finnish)	0.00195%	51,261
African / African-American	0.00133%	74,914

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.Ser2389=
Coding: c.7167C>T
MANE Select: NM_206933
dbSNP: rs200243588
Type: single nucleotide variant
Location: chr1:215934749 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2389: the fibronectin type-iii 10 domain

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

Disease context

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

Also linked: Usher syndrome type 2A

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

USH2A p.Ser2389Arg Uncertain significance ★ ⚠ same residue
USH2A p.Ser2389Asn 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-ser2389 (accessed [today's date]).

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