Is CRIP1 p.Lys30Arg (c.89A>G) pathogenic?

CRIP1 p.Lys30Arg (c.89A>G) is classified Uncertain significance in CRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely benign (0.0771); Ultra-rare (popmax 0.0823%, sas).

How common is CRIP1 p.Lys30Arg (c.89A>G) in the general population?

CRIP1 p.Lys30Arg (c.89A>G) is ultra-rare (popmax 0.0823%, sas) (gnomAD).

What do computational predictors say about CRIP1 p.Lys30Arg (c.89A>G)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

CRIP1 p.Lys30Arg

c.89A>G · rs587683805 · VCV2230292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0823%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.43	donor gain · deltas
Pangolin	Δ0.20	gain · loss 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.9	GERP -0.99, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 1,248 bp · p 0.039 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.0823% South Asian · 75/91,084 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0617%

Overall 0.00539% 87/1,613,318 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0823%	1,214
Remaining individualsnot grpmax-eligible	0.016%	6,249
African / African-American	0.00133%	75,068
European (non-Finnish)	8.47e-05%	1,179,999

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.Lys30Arg
Coding: c.89A>G
MANE Select: NM_001311
dbSNP: rs587683805
Type: single nucleotide variant
Location: chr14:105488214 (GRCh38)
Gene constraint: LOEUF 1.447 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.41
Residue 30: the lim zinc-binding domain

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

Similar variants

CRIP1 p.Lys30Glu Uncertain significance ★ ⚠ same residue
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

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-lys30arg (accessed [today's date]).

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