Is RPGRIP1 p.Pro96Ser (c.286C>T) pathogenic?

RPGRIP1 p.Pro96Ser (c.286C>T) is classified Uncertain significance in RPGRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0753); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with RPGRIP1 p.Pro96Ser (c.286C>T)?

RPGRIP1 p.Pro96Ser (c.286C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RPGRIP1 p.Pro96Ser (c.286C>T) in the general population?

RPGRIP1 p.Pro96Ser (c.286C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about RPGRIP1 p.Pro96Ser (c.286C>T)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

RPGRIP1 p.Pro96Ser

c.286C>T · VCV4629432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -2.3, phastCons 0.004
Regional constraint	o/e 0.96	unconstrained · MANE · 63 kb · p 0.13 · regional, not allelic
Overall
CADD	5.402	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,044 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,612,366 alleles · very rare exomes 2/1,460,136 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,522
African / African-American	0.00134%	74,894

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.Pro96Ser
Coding: c.286C>T
MANE Select: NM_020366
Type: single nucleotide variant
Location: chr14:21301033 (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 96: a UniProt-annotated variant site (in)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RPGRIP1 p.Pro96Gln Benign ★★ same residue
RPGRIP1 p.Ala1126Val Uncertain significance ★★ ⚠ same condition
RPGRIP1 p.Ala228Val Uncertain significance ★★ ⚠ same condition
RPGRIP1 p.Ala403Val Uncertain significance ★★ ⚠ same condition
RPGRIP1 p.Ala641Thr Uncertain significance ★★ ⚠ same condition
RPGRIP1 p.Arg110Trp Uncertain significance ★★ ⚠ same condition
RPGRIP1 p.Arg1189Gln Uncertain significance ★★ ⚠ same condition
RPGRIP1 p.Arg1190Ser Uncertain significance ★★ ⚠ 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-pro96ser (accessed [today's date]).

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