Is USH2A p.Ser5039= (c.15117C>T) pathogenic?

USH2A p.Ser5039= (c.15117C>T) is classified Likely benign in USH2A (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.04%, afr); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Ser5039= (c.15117C>T)?

USH2A p.Ser5039= (c.15117C>T) is associated with Usher syndrome type 2A (ClinVar).

How common is USH2A p.Ser5039= (c.15117C>T) in the general population?

USH2A p.Ser5039= (c.15117C>T) is ultra-rare (popmax 0.04%, afr) (gnomAD).

USH2A p.Ser5039=

c.15117C>T · rs148499621 · VCV856648

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -4.2
Overall
CADD	0.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.04% African / African-American · 30/75,046 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00229% 37/1,614,202 alleles · ultra-rare exomes 19/1,461,892 · genomes 18/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,502
Admixed American	0.005%	20,008
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000254%	393,348

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.Ser5039=
Coding: c.15117C>T
MANE Select: NM_206933
dbSNP: rs148499621
Type: single nucleotide variant
Location: chr1:215634639 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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.Ser5039del Uncertain significance same residue
USH2A p.Ser5039Arg 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-ser5039 (accessed [today's date]).

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