Is CRB1 p.Ala511= (c.1533C>T) pathogenic?

CRB1 p.Ala511= (c.1533C>T) is classified Conflicting classifications of pathogenicity in CRB1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Low-frequency (popmax 2.11%, sas); Associated with retinitis pigmentosa.

What condition is associated with CRB1 p.Ala511= (c.1533C>T)?

CRB1 p.Ala511= (c.1533C>T) is associated with retinitis pigmentosa, pigmented paravenous retinochoroidal atrophy, retinitis pigmentosa 12 (ClinVar).

How common is CRB1 p.Ala511= (c.1533C>T) in the general population?

CRB1 p.Ala511= (c.1533C>T) is low-frequency (popmax 2.11%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

CRB1 p.Ala511=

c.1533C>T · rs142224492 · VCV166957

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.11%, sas)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	GERP -2, phastCons 0.97
Overall
CADD	6.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.11% South Asian · 1,926/91,080 alleles

Filtering AF 2.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 2%

Overall 0.171% 2,761/1,614,190 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.11%	47
Middle Eastern	0.61%	164
Ashkenazi Jewishnot grpmax-eligible	0.334%	299
Remaining individualsnot grpmax-eligible	0.203%	492
Admixed American	0.0933%	1,072
European (non-Finnish)	0.0422%	2,370
African / African-American	0.0147%	6,822
Finnishnot grpmax-eligible	0.00937%	10,673
East Asian	0.00223%	44,882

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: CRB1
Protein: p.Ala511=
Coding: c.1533C>T
MANE Select: NM_201253
dbSNP: rs142224492
Type: single nucleotide variant
Location: chr1:197421361 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 511: 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

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

Also linked: pigmented paravenous retinochoroidal atrophy retinitis pigmentosa 12 Leber congenital amaurosis 8 Leber congenital amaurosis

For Retinitis pigmentosa (Orphanet):

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

Similar variants

CRB1 c.1172-2A>G Likely pathogenic ★★ same condition
CRB1 c.2128+1G>C Pathogenic/Likely pathogenic ★★ same condition
CRB1 c.2129-1G>A Pathogenic/Likely pathogenic ★★ same condition
CRB1 c.2129-1G>C Pathogenic ★★ same condition
CRB1 c.2129-2A>G Pathogenic ★★ same condition
CRB1 c.2676+1G>A Likely pathogenic ★★ same condition
CRB1 c.2676+1G>T Pathogenic/Likely pathogenic ★★ same condition
CRB1 c.2842+5G>A 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-ala511 (accessed [today's date]).

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