Is USH2A p.Phe4602Ser (c.13805T>C) pathogenic?

USH2A p.Phe4602Ser (c.13805T>C) is classified Likely benign in USH2A (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-28). AlphaMissense: likely benign (0.2053); Ultra-rare (popmax 0.0406%, sas); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Phe4602Ser (c.13805T>C)?

USH2A p.Phe4602Ser (c.13805T>C) is associated with Usher syndrome type 2A (ClinVar).

How common is USH2A p.Phe4602Ser (c.13805T>C) in the general population?

USH2A p.Phe4602Ser (c.13805T>C) is ultra-rare (popmax 0.0406%, sas) (gnomAD).

What do computational predictors say about USH2A p.Phe4602Ser (c.13805T>C)?

AlphaMissense predicts likely benign (score 0.2053) — an in-silico prediction, not a clinical call.

USH2A p.Phe4602Ser

c.13805T>C · rs574442439 · VCV968059

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Usher syndrome type 2A

Computational evidence

Protein change
AlphaMissense	0.2053	likely benign
REVEL	0.201	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.63, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 797 kb · p 0.00011 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0406% South Asian · 37/91,044 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.0026% 42/1,614,048 alleles · ultra-rare exomes 40/1,461,788 · genomes 2/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0406%	2,461
Remaining individualsnot grpmax-eligible	0.008%	12,500

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.Phe4602Ser
Coding: c.13805T>C
MANE Select: NM_206933
dbSNP: rs574442439
Type: single nucleotide variant
Location: chr1:215674106 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4602: the fibronectin type-iii 31 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.Phe4602Leu Pathogenic ★ ⚠ same residue
USH2A p.Phe4602= Likely benign ★ 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-phe4602ser (accessed [today's date]).

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