Is RPGRIP1 p.Pro175= (c.525A>G) pathogenic?

RPGRIP1 p.Pro175= (c.525A>G) is classified Benign in RPGRIP1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 25.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with cone-rod dystrophy 13.

What condition is associated with RPGRIP1 p.Pro175= (c.525A>G)?

RPGRIP1 p.Pro175= (c.525A>G) 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.Pro175=

Q: How common is RPGRIP1 p.Pro175= (c.525A>G) in the general population?

RPGRIP1 p.Pro175= (c.525A>G) is common (popmax 25.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.525A>G · rs17792599 · VCV99826

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 25.3%, mid) — 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.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4	GERP -3.2
Overall
CADD	2.513	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.3% Middle Eastern · 1,511/5,976 alleles

Filtering AF 24.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.8%

Overall 17.1% 271,425/1,583,980 alleles · common exomes 247,211/1,431,778 · genomes 24,214/152,202 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	39.4%	3
Middle Easterngrpmax	25.3%	4
Amishnot grpmax-eligible	23.1%	4
Remaining individualsnot grpmax-eligible	19%	5
European (non-Finnish)	18%	6
Admixed American	13%	8
African / African-American	12.8%	8
South Asian	11.9%	8
Finnishnot grpmax-eligible	10.7%	9
East Asian	8.66%	12

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro175=
Coding: c.525A>G
MANE Select: NM_020366
dbSNP: rs17792599
Type: single nucleotide variant
Location: chr14:21302522 (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 175: the 'disordered' 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 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
RPGRIP1 c.3617+1G>A 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-pro175 (accessed [today's date]).

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