Is PCDH15 p.Pro320= (c.960A>G) pathogenic?

PCDH15 p.Pro320= (c.960A>G) is classified Benign in PCDH15 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). Common (popmax 8.08%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 1.

What condition is associated with PCDH15 p.Pro320= (c.960A>G)?

PCDH15 p.Pro320= (c.960A>G) is associated with Usher syndrome type 1, Usher syndrome type 1F (ClinVar).

How is Usher syndrome inherited?

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

PCDH15 p.Pro320=

Q: How common is PCDH15 p.Pro320= (c.960A>G) in the general population?

PCDH15 p.Pro320= (c.960A>G) is common (popmax 8.08%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.960A>G · rs41274634 · VCV46513

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 8.08%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Usher syndrome type 1

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 -1.7	GERP -2.7
Overall
CADD	4.165	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.08% South Asian · 7,354/91,044 alleles

Filtering AF 7.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.86%

Overall 2.92% 47,180/1,613,256 alleles · common exomes 43,321/1,461,000 · genomes 3,859/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	8.08%	12
Amishnot grpmax-eligible	3.62%	28
Admixed American	3.5%	29
European (non-Finnish)	2.8%	36
Remaining individualsnot grpmax-eligible	2.65%	38
Middle Eastern	2.38%	42
African / African-American	2.05%	49
Finnishnot grpmax-eligible	1.62%	62
Ashkenazi Jewishnot grpmax-eligible	0.95%	105
East Asian	0.132%	760

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: PCDH15
Protein: p.Pro320=
Coding: c.960A>G
MANE Select: NM_001384140
dbSNP: rs41274634
Type: single nucleotide variant
Location: chr10:54236848 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.05 · 8 PDB
Residue 320: an α-helix; the cadherin 3 domain

Full PCDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1F

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

PCDH15 c.1306-2A>G Likely pathogenic ★★ same condition
PCDH15 c.1440+2T>C Likely pathogenic ★★ same condition
PCDH15 c.1441-2A>C Likely pathogenic ★★ same condition
PCDH15 c.158-2A>T Pathogenic/Likely pathogenic ★★ same condition
PCDH15 c.1784+1G>T Pathogenic/Likely pathogenic ★★ same condition
PCDH15 c.1917+1G>A Likely pathogenic ★★ same condition
PCDH15 c.1918-1G>A Likely pathogenic ★★ same condition
PCDH15 c.1997+1G>A Pathogenic/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/pcdh15-p-pro320 (accessed [today's date]).

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