Is CRB1 p.Pro617Gln (c.1850C>A) pathogenic?

CRB1 p.Pro617Gln (c.1850C>A) is classified Conflicting classifications of pathogenicity in CRB1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-01-01). AlphaMissense: likely benign (0.2825); Absent from gnomAD v4.1; Associated with optic atrophy.

What condition is associated with CRB1 p.Pro617Gln (c.1850C>A)?

CRB1 p.Pro617Gln (c.1850C>A) is associated with optic atrophy, cone-rod dystrophy (ClinVar).

How common is CRB1 p.Pro617Gln (c.1850C>A) in the general population?

CRB1 p.Pro617Gln (c.1850C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRB1 p.Pro617Gln (c.1850C>A)?

AlphaMissense predicts likely benign (score 0.2825) — an in-silico prediction, not a clinical call.

CRB1 p.Pro617Gln

c.1850C>A · rs1057519162 · VCV374588

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2825 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

optic atrophy

Computational evidence

Protein change
AlphaMissense	0.2825	likely benign
REVEL	0.488	indeterminate
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 209 kb · p 0.78 · regional, not allelic
Overall
CADD	23.2	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.Pro617Gln
Coding: c.1850C>A
MANE Select: NM_201253
dbSNP: rs1057519162
Type: single nucleotide variant
Location: chr1:197421678 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 617: a UniProt-annotated variant site (in lca8); the laminin g-like 1 domain

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

Disease context

optic atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone-rod dystrophy

Similar variants

CRB1 p.Arg764Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CRB1 p.Cys1294Tyr Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Cys928Arg Likely pathogenic ★ same condition
CRB1 p.Asn894Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
CRB1 p.Lys994Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
CRB1 p.Ala1362Ser Uncertain significance ⚠ same condition
CRB1 p.Leu613_Gly614insVal Uncertain significance ★★ same condition
CRB1 p.Val320fs 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-pro617gln (accessed [today's date]).

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