Is CRIP1 p.Glu72Lys (c.214G>A) pathogenic?

CRIP1 p.Glu72Lys (c.214G>A) is classified Uncertain significance in CRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: likely pathogenic (0.7105); Ultra-rare (popmax 0.0546%, eas).

How common is CRIP1 p.Glu72Lys (c.214G>A) in the general population?

CRIP1 p.Glu72Lys (c.214G>A) is ultra-rare (popmax 0.0546%, eas) (gnomAD).

What do computational predictors say about CRIP1 p.Glu72Lys (c.214G>A)?

AlphaMissense predicts likely pathogenic (score 0.7105) — an in-silico prediction, not a clinical call.

CRIP1 p.Glu72Lys

c.214G>A · rs200533449 · VCV2514932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7105 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7105	likely pathogenic
REVEL	0.653	pathogenic-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 1,248 bp · p 0.039 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.0546% East Asian · 24/43,974 alleles

Filtering AF 0.0376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.032%

Overall 0.0027% 43/1,594,768 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0546%	1,832
Ashkenazi Jewishnot grpmax-eligible	0.00692%	14,452
Admixed American	0.00339%	29,475
Remaining individualsnot grpmax-eligible	0.00324%	30,838
South Asian	0.00222%	44,957
African / African-American	0.00136%	73,606
European (non-Finnish)	0.000854%	117,120

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: CRIP1
Protein: p.Glu72Lys
Coding: c.214G>A
MANE Select: NM_001311
dbSNP: rs200533449
Type: single nucleotide variant
Location: chr14:105488491 (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-glu72lys (accessed [today's date]).

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