Is RPGRIP1 p.Phe745= (c.2235C>T) pathogenic?

RPGRIP1 p.Phe745= (c.2235C>T) is classified Likely benign in RPGRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-07). Very rare (popmax 0.00508%, amr); Associated with cone-rod dystrophy 13.

What condition is associated with RPGRIP1 p.Phe745= (c.2235C>T)?

RPGRIP1 p.Phe745= (c.2235C>T) is associated with cone-rod dystrophy 13, Leber congenital amaurosis 6 (ClinVar).

How common is RPGRIP1 p.Phe745= (c.2235C>T) in the general population?

RPGRIP1 p.Phe745= (c.2235C>T) is very rare (popmax 0.00508%, amr) (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.Phe745=

c.2235C>T · rs767808334 · VCV1532736

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00508%, amr)

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	all four deltas below 0.2 · C>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.5	GERP -3.3
Overall
CADD	1.919	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00508% Admixed American · 3/59,038 alleles

Filtering AF 0.00135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000674%

Overall 0.00112% 18/1,610,168 alleles · very rare exomes 16/1,457,966 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00508%	19,679
African / African-American	0.00268%	37,327
South Asian	0.00221%	45,229
Remaining individualsnot grpmax-eligible	0.00161%	62,248
European (non-Finnish)	0.000848%	117,859

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.Phe745=
Coding: c.2235C>T
MANE Select: NM_020366
dbSNP: rs767808334
Type: single nucleotide variant
Location: chr14:21325251 (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 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-phe745 (accessed [today's date]).

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