Is USH2A p.Val3612= (c.10836C>A) pathogenic?

USH2A p.Val3612= (c.10836C>A) is classified Benign/Likely benign in USH2A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 9.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Val3612= (c.10836C>A)?

USH2A p.Val3612= (c.10836C>A) 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.Val3612=

Q: How common is USH2A p.Val3612= (c.10836C>A) in the general population?

USH2A p.Val3612= (c.10836C>A) is common (popmax 9.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.10836C>A · rs61276761 · VCV48359

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 9.5%, 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 5	GERP 0.15, phastCons 1
Overall
CADD	4.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.5% African / African-American · 7,120/74,934 alleles

Filtering AF 9.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.24%

Overall 0.505% 8,143/1,614,020 alleles · common exomes 4,007/1,461,882 · genomes 4,136/152,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.5%	11
Admixed American	0.687%	146
Remaining individualsnot grpmax-eligible	0.685%	146
Middle Eastern	0.297%	337
European (non-Finnish)	0.0132%	7,564
South Asian	0.00988%	10,120

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.Val3612=
Coding: c.10836C>A
MANE Select: NM_206933
dbSNP: rs61276761
Type: single nucleotide variant
Location: chr1:215779946 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3612: the fibronectin type-iii 21 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 p.Val3612Ile 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
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-val3612 (accessed [today's date]).

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