Is CRIP1 p.Phe76Leu (c.228C>G) pathogenic?

CRIP1 p.Phe76Leu (c.228C>G) is classified Uncertain significance in CRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely pathogenic (0.9519); Absent from gnomAD v4.1.

How common is CRIP1 p.Phe76Leu (c.228C>G) in the general population?

CRIP1 p.Phe76Leu (c.228C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRIP1 p.Phe76Leu (c.228C>G)?

AlphaMissense predicts likely pathogenic (score 0.9519) — an in-silico prediction, not a clinical call.

CRIP1 p.Phe76Leu

c.228C>G · rs2545286413 · VCV3077450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9519 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9519	likely pathogenic
REVEL	0.382	indeterminate
SaProt	LLR -11.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 1,248 bp · p 0.039 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CRIP1
Protein: p.Phe76Leu
Coding: c.228C>G
MANE Select: NM_001311
dbSNP: rs2545286413
Type: single nucleotide variant
Location: chr14:105488505 (GRCh38)
Gene constraint: LOEUF 1.447 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.41

Full CRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRIP1 p.Cys52Phe Benign ★★ same type
CRIP1 p.Ala58Pro Uncertain significance ★ ⚠ same type
CRIP1 p.Arg16Thr Uncertain significance ★ ⚠ same type
CRIP1 p.Arg26Gln Uncertain significance ★ ⚠ same type
CRIP1 p.Arg26Trp Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Gln Uncertain significance ★ same type
CRIP1 p.Arg68Gly Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Pro Uncertain significance ★ ⚠ same type

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/crip1-p-phe76leu (accessed [today's date]).

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