Is RPGRIP1 p.Pro599= (c.1797G>A) pathogenic?

RPGRIP1 p.Pro599= (c.1797G>A) is classified Benign in RPGRIP1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 27.2%, sas) — too common for a highly-penetrant pathogenic allele; Associated with cone-rod dystrophy 13.

What condition is associated with RPGRIP1 p.Pro599= (c.1797G>A)?

RPGRIP1 p.Pro599= (c.1797G>A) is associated with cone-rod dystrophy 13, Leber congenital amaurosis 6 (ClinVar).

How is Cone rod dystrophy inherited?

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

RPGRIP1 p.Pro599=

Q: How common is RPGRIP1 p.Pro599= (c.1797G>A) in the general population?

RPGRIP1 p.Pro599= (c.1797G>A) is common (popmax 27.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1797G>A · rs9322965 · VCV99812

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 27.2%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

cone-rod dystrophy 13

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.139	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP 0.89
Overall
CADD	6.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.2% South Asian · 24,792/91,064 alleles

Filtering AF 26.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.8%

Overall 22.9% 369,137/1,613,316 alleles · common exomes 335,615/1,461,174 · genomes 33,522/152,142 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	27.2%	4
Finnishnot grpmax-eligible	26.1%	4
European (non-Finnish)	23.9%	4
Middle Eastern	23.8%	4
Amishnot grpmax-eligible	23.1%	4
African / African-American	22.7%	4
Remaining individualsnot grpmax-eligible	22.5%	4
Ashkenazi Jewishnot grpmax-eligible	17.9%	6
Admixed American	12.1%	8
East Asian	1.94%	51

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.Pro599=
Coding: c.1797G>A
MANE Select: NM_020366
dbSNP: rs9322965
Type: single nucleotide variant
Location: chr14:21324652 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.60 · 1 PDB

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.Pro599Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro599 (accessed [today's date]).

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