Is CRB2 p.Ala487Val (c.1460C>T) pathogenic?

CRB2 p.Ala487Val (c.1460C>T) is classified Uncertain significance in CRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.1121); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CRB2 p.Ala487Val (c.1460C>T)?

CRB2 p.Ala487Val (c.1460C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CRB2 p.Ala487Val (c.1460C>T) in the general population?

CRB2 p.Ala487Val (c.1460C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CRB2 p.Ala487Val (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

CRB2 p.Ala487Val

c.1460C>T · rs555576780 · VCV3077259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -8.89	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 0.22	GERP -0.22, phastCons 0.009
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.85 · regional, not allelic
Overall
CADD	15.0	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 0.00446% East Asian · 2/44,892 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,613,434 alleles · very rare exomes 0/1,461,074 · genomes 2/152,360 · joint denominator

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: CRB2
Protein: p.Ala487Val
Coding: c.1460C>T
MANE Select: NM_173689
dbSNP: rs555576780
Type: single nucleotide variant
Location: chr9:123370513 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 487: the laminin g-like 1 domain; a UniProt-annotated variant site (in fsgs9; uncertain significance)

Full CRB2 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

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CRB2 p.Ala26Asp Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala325Val Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala80Thr Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala887Thr Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala914Val 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/crb2-p-ala487val (accessed [today's date]).

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