Is USH2A p.Ser4772Phe (c.14315C>T) pathogenic?

USH2A p.Ser4772Phe (c.14315C>T) is classified Benign/Likely benign in USH2A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.1663); Low-frequency (popmax 1.2%, afr); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Ser4772Phe (c.14315C>T)?

USH2A p.Ser4772Phe (c.14315C>T) is associated with Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Ser4772Phe (c.14315C>T) in the general population?

USH2A p.Ser4772Phe (c.14315C>T) is low-frequency (popmax 1.2%, afr) (gnomAD).

What do computational predictors say about USH2A p.Ser4772Phe (c.14315C>T)?

AlphaMissense predicts likely benign (score 0.1663) — an in-silico prediction, not a clinical call.

USH2A p.Ser4772Phe

c.14315C>T · rs149222801 · VCV48434

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1663 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, afr)

Conditions

Usher syndrome type 2A

Computational evidence

Protein change
AlphaMissense	0.1663	likely benign
REVEL	0.361	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 797 kb · p 0.00011 · regional, not allelic
Overall
CADD	21.0	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 1.2% African / African-American · 898/75,044 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0593% 958/1,614,176 alleles · low-frequency exomes 490/1,461,886 · genomes 468/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.2%	84
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.04%	2,501
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
South Asian	0.0011%	91,082
European (non-Finnish)	0.000508%	196,674

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.Ser4772Phe
Coding: c.14315C>T
MANE Select: NM_206933
dbSNP: rs149222801
Type: single nucleotide variant
Location: chr1:215650620 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4772: the fibronectin type-iii 33 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

Also linked: retinitis pigmentosa 39

Similar variants

USH2A p.Ser4772= 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
USH2A p.Asn346His 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-ser4772phe (accessed [today's date]).

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