Is USH2A p.Pro3969= (c.11907A>T) pathogenic?

USH2A p.Pro3969= (c.11907A>T) is classified Benign in USH2A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Pro3969= (c.11907A>T)?

USH2A p.Pro3969= (c.11907A>T) is associated with retinitis pigmentosa 39, Usher syndrome type 2A (ClinVar).

How is Retinitis pigmentosa inherited?

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

USH2A p.Pro3969=

Q: How common is USH2A p.Pro3969= (c.11907A>T) in the general population?

USH2A p.Pro3969= (c.11907A>T) is common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.11907A>T · rs61635304 · VCV48384

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

retinitis pigmentosa 39

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 -3.2	GERP -4.4
Overall
CADD	1.728	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.5% African / African-American · 10,118/74,974 alleles

Filtering AF 13.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.2%

Overall 0.823% 13,292/1,614,098 alleles · common exomes 7,151/1,461,882 · genomes 6,141/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.5%	7
Admixed American	1.55%	65
Middle Eastern	1.49%	67
Remaining individualsnot grpmax-eligible	1.27%	79
Amishnot grpmax-eligible	1.21%	83
Ashkenazi Jewishnot grpmax-eligible	1.17%	85
European (non-Finnish)	0.0818%	1,223
South Asian	0.0428%	2,335
East Asian	0.00223%	44,878
Finnishnot grpmax-eligible	0.00156%	64,038

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.Pro3969=
Coding: c.11907A>T
MANE Select: NM_206933
dbSNP: rs61635304
Type: single nucleotide variant
Location: chr1:215728189 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3969: the fibronectin type-iii 25 domain

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

Disease context

retinitis pigmentosa 39 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 2A

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

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
USH2A p.Asn4292Asp 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-pro3969 (accessed [today's date]).

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