Is CRIP2 p.Lys205Arg (c.614A>G) pathogenic?

CRIP2 p.Lys205Arg (c.614A>G) is classified Uncertain significance in CRIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely benign (0.0743); Absent from gnomAD v4.1.

How common is CRIP2 p.Lys205Arg (c.614A>G) in the general population?

CRIP2 p.Lys205Arg (c.614A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRIP2 p.Lys205Arg (c.614A>G)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

CRIP2 p.Lys205Arg

c.614A>G · VCV3497090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.66	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 4.9	GERP 0.74, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 4,787 bp · p 4.9e-07 · regional, not allelic
Overall
CADD	18.34	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

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: CRIP2
Protein: p.Lys205Arg
Coding: c.614A>G
MANE Select: NM_001312
Type: single nucleotide variant
Location: chr14:105479640 (GRCh38)
Gene constraint: LOEUF 1.553 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.78 · 1 PDB

Full CRIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRIP2 p.Ala113Val Uncertain significance ★ ⚠ same type
CRIP2 p.Ala166Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Ala82Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Ala96Gly Uncertain significance ★ ⚠ same type
CRIP2 p.Ala98Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Arg128His Uncertain significance ★ ⚠ same type
CRIP2 p.Arg148Gly Uncertain significance ★ ⚠ same type
CRIP2 p.Arg148Trp 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/crip2-p-lys205arg (accessed [today's date]).

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