Is CRIP3 p.Val174Ile (c.520G>A) pathogenic?

CRIP3 p.Val174Ile (c.520G>A) is classified Likely benign in CRIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.055); Ultra-rare (popmax 0.0134%, eas).

How common is CRIP3 p.Val174Ile (c.520G>A) in the general population?

CRIP3 p.Val174Ile (c.520G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CRIP3 p.Val174Ile (c.520G>A)?

AlphaMissense predicts likely benign (score 0.055) — an in-silico prediction, not a clinical call.

CRIP3 p.Val174Ile

c.520G>A · VCV3836368

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.055 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.055	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -9.51	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 2.9	GERP -2.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,975 bp · p 0.92 · regional, not allelic
Overall
CADD	15.03	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

Grpmax group 0.0134% East Asian · 6/44,882 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00161% 26/1,613,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
South Asian	0.00329%	30,356
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00136%	73,746

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: CRIP3
Protein: p.Val174Ile
Coding: c.520G>A
MANE Select: NM_206922
Type: single nucleotide variant
Location: chr6:43306100 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 174: the lim zinc-binding 2 domain

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-val174ile (accessed [today's date]).

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