Is CRB2 p.Phe688Ser (c.2063T>C) pathogenic?

CRB2 p.Phe688Ser (c.2063T>C) is classified Uncertain significance in CRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely pathogenic (0.6677); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CRB2 p.Phe688Ser (c.2063T>C)?

CRB2 p.Phe688Ser (c.2063T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CRB2 p.Phe688Ser (c.2063T>C) in the general population?

CRB2 p.Phe688Ser (c.2063T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRB2 p.Phe688Ser (c.2063T>C)?

AlphaMissense predicts likely pathogenic (score 0.6677) — an in-silico prediction, not a clinical call.

CRB2 p.Phe688Ser

c.2063T>C · VCV3836231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6677 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6677	likely pathogenic
REVEL	0.278	benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 0.98
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.85 · regional, not allelic
Overall
CADD	22.4	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: CRB2
Protein: p.Phe688Ser
Coding: c.2063T>C
MANE Select: NM_173689
Type: single nucleotide variant
Location: chr9:123371205 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 688: the laminin g-like 2 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

CRB2 p.Phe688Tyr Uncertain significance ★ ⚠ same residue
CRB2 p.Ala1042Thr Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala1266Pro Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala228Thr Uncertain significance ★★ ⚠ same condition
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

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-phe688ser (accessed [today's date]).

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