Is RPGRIP1 p.Pro1104= (c.3312A>G) pathogenic?

RPGRIP1 p.Pro1104= (c.3312A>G) is classified Likely benign in RPGRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). Very rare (popmax 8.5e-05%, nfe); Associated with cone-rod dystrophy 13.

What condition is associated with RPGRIP1 p.Pro1104= (c.3312A>G)?

RPGRIP1 p.Pro1104= (c.3312A>G) is associated with cone-rod dystrophy 13, Leber congenital amaurosis 6 (ClinVar).

How common is RPGRIP1 p.Pro1104= (c.3312A>G) in the general population?

RPGRIP1 p.Pro1104= (c.3312A>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

How is Cone rod dystrophy inherited?

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

RPGRIP1 p.Pro1104=

c.3312A>G · rs776206959 · VCV2159871

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

cone-rod dystrophy 13

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.022	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42	GERP -0.73
Overall
CADD	3.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,848 alleles

Overall 6.22e-05% 1/1,606,740 alleles · very rare exomes 1/1,456,972 · genomes 0/149,768 · joint denominator

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: RPGRIP1
Protein: p.Pro1104=
Coding: c.3312A>G
MANE Select: NM_020366
dbSNP: rs776206959
Type: single nucleotide variant
Location: chr14:21334678 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.60 · 1 PDB
Residue 1104: the 'disordered' region; the 'interaction with rpgr' region

Full RPGRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cone-rod dystrophy 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leber congenital amaurosis 6

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

RPGRIP1 p.Pro1104Ala Uncertain significance ★ ⚠ same residue
RPGRIP1 c.1467+1G>A Pathogenic/Likely pathogenic ★★ same condition
RPGRIP1 c.1468-2A>G Pathogenic/Likely pathogenic ★★ same condition
RPGRIP1 c.218+1G>T Likely pathogenic ★★ same condition
RPGRIP1 c.2367+1G>A Pathogenic ★★ same condition
RPGRIP1 c.2368-2A>G Pathogenic/Likely pathogenic ★★ same condition
RPGRIP1 c.2711-2A>G Pathogenic ★★ same condition
RPGRIP1 c.2895+1G>T 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/rpgrip1-p-pro1104 (accessed [today's date]).

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