Is CRIP3 p.Thr118Ile (c.353C>T) pathogenic?

CRIP3 p.Thr118Ile (c.353C>T) is classified Uncertain significance in CRIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.2653); Absent from gnomAD v4.1.

How common is CRIP3 p.Thr118Ile (c.353C>T) in the general population?

CRIP3 p.Thr118Ile (c.353C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRIP3 p.Thr118Ile (c.353C>T)?

AlphaMissense predicts likely benign (score 0.2653) — an in-silico prediction, not a clinical call.

CRIP3 p.Thr118Ile

c.353C>T · VCV3497095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2653	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -11.55	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,975 bp · p 0.92 · regional, not allelic
Overall
CADD	24.7	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: CRIP3
Protein: p.Thr118Ile
Coding: c.353C>T
MANE Select: NM_206922
Type: single nucleotide variant
Location: chr6:43306493 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81

Full CRIP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRIP3 p.Ala60Thr Uncertain significance ★ ⚠ same type
CRIP3 p.Arg146Gln Uncertain significance ★ ⚠ same type
CRIP3 p.Arg50Trp Uncertain significance ★ ⚠ same type
CRIP3 p.Asn78Ser Uncertain significance ★ ⚠ same type
CRIP3 p.Cys127Tyr Uncertain significance ★ ⚠ same type
CRIP3 p.Cys151Tyr Uncertain significance ★ ⚠ same type
CRIP3 p.Cys154Phe Uncertain significance ★ ⚠ same type
CRIP3 p.Cys5Arg 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/crip3-p-thr118ile (accessed [today's date]).

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