Is CRB1 p.Cys707Phe (c.2120G>T) pathogenic?

CRB1 p.Cys707Phe (c.2120G>T) is classified Likely pathogenic in CRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-30). AlphaMissense: likely pathogenic (0.9132); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with CRB1 p.Cys707Phe (c.2120G>T)?

CRB1 p.Cys707Phe (c.2120G>T) is associated with retinitis pigmentosa (ClinVar).

How common is CRB1 p.Cys707Phe (c.2120G>T) in the general population?

CRB1 p.Cys707Phe (c.2120G>T) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about CRB1 p.Cys707Phe (c.2120G>T)?

AlphaMissense predicts likely pathogenic (score 0.9132) — an in-silico prediction, not a clinical call.

CRB1 p.Cys707Phe

c.2120G>T · VCV3385322

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9132 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.9132	likely pathogenic ✓ concordant with ClinVar · top 3% in CRB1
REVEL	0.697	pathogenic-leaning
SaProt	LLR -14.82	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 209 kb · p 0.78 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRB1
Protein: p.Cys707Phe
Coding: c.2120G>T
MANE Select: NM_201253
Type: single nucleotide variant
Location: chr1:197421948 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 707: a UniProt-annotated variant site (in lca8); the egf-like 12 domain; a disulfide bond

Full CRB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CRB1 p.Arg1331Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CRB1 p.Arg764Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CRB1 p.Cys394Ter Pathogenic ★★ same condition
CRB1 p.Cys896Ter Pathogenic ★★ same condition
CRB1 p.Cys948Tyr Pathogenic ★★ same condition
CRB1 p.Gly1226Ter Pathogenic ★★ same condition
CRB1 p.Gly477Arg Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Gly615Val Pathogenic/Likely 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/crb1-p-cys707phe (accessed [today's date]).

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