Is RPGRIP1 p.Ser792= (c.2376G>A) pathogenic?

RPGRIP1 p.Ser792= (c.2376G>A) is classified Conflicting classifications of pathogenicity in RPGRIP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-11). Rare (popmax 0.573%, afr); Associated with Leber congenital amaurosis 6.

What condition is associated with RPGRIP1 p.Ser792= (c.2376G>A)?

RPGRIP1 p.Ser792= (c.2376G>A) is associated with Leber congenital amaurosis 6, cone-rod dystrophy 13 (ClinVar).

How common is RPGRIP1 p.Ser792= (c.2376G>A) in the general population?

RPGRIP1 p.Ser792= (c.2376G>A) is rare (popmax 0.573%, afr) (gnomAD).

How is Leber congenital amaurosis inherited?

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

RPGRIP1 p.Ser792=

c.2376G>A · rs185667326 · VCV502550

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.573%, afr)

Conditions

Leber congenital amaurosis 6

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 -3.1	GERP -3.3
Overall
CADD	0.979	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.573% African / African-American · 430/75,008 alleles

Filtering AF 0.529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.511%

Overall 0.0305% 492/1,611,520 alleles · rare exomes 239/1,459,252 · genomes 253/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.573%	174
Middle Eastern	0.0331%	3,024
Remaining individualsnot grpmax-eligible	0.0273%	3,670
Admixed American	0.025%	3,996
Finnishnot grpmax-eligible	0.00313%	31,980
East Asian	0.00223%	44,870
European (non-Finnish)	0.00204%	49,086
South Asian	0.0011%	90,868

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.Ser792=
Coding: c.2376G>A
MANE Select: NM_020366
dbSNP: rs185667326
Type: single nucleotide variant
Location: chr14:21325839 (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 792: the c2 domain

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

Disease context

Leber congenital amaurosis 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone-rod dystrophy 13

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
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-ser792 (accessed [today's date]).

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