Is USH2A p.Ser3822Pro (c.11464T>C) pathogenic?

USH2A p.Ser3822Pro (c.11464T>C) is classified Conflicting classifications of pathogenicity in USH2A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0622); Rare (popmax 0.11%, eas); Associated with inherited retinal dystrophy.

What condition is associated with USH2A p.Ser3822Pro (c.11464T>C)?

USH2A p.Ser3822Pro (c.11464T>C) is associated with inherited retinal dystrophy, Usher syndrome type 2A (ClinVar).

How common is USH2A p.Ser3822Pro (c.11464T>C) in the general population?

USH2A p.Ser3822Pro (c.11464T>C) is rare (popmax 0.11%, eas) (gnomAD).

What do computational predictors say about USH2A p.Ser3822Pro (c.11464T>C)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

USH2A p.Ser3822Pro

c.11464T>C · rs201961789 · VCV869192

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.051	moderately 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 0.34	GERP -3.1, phastCons 0.01
Regional constraint	o/e 1.05	unconstrained · MANE · 797 kb · p 0.00011 · regional, not allelic
Overall
CADD	3.705	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 0.11% East Asian · 49/44,742 alleles

Filtering AF 0.0851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0764%

Overall 0.00323% 52/1,612,182 alleles · rare exomes 46/1,461,300 · genomes 6/150,882 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.11%	913
Remaining individualsnot grpmax-eligible	0.0032%	31,220
European (non-Finnish)	8.48e-05%	1,179,466

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.Ser3822Pro
Coding: c.11464T>C
MANE Select: NM_206933
dbSNP: rs201961789
Type: single nucleotide variant
Location: chr1:215743261 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3822: the fibronectin type-iii 23 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 2A

Similar variants

USH2A p.Ser3822= 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-ser3822pro (accessed [today's date]).

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