Is CRIP3 p.Val67Leu (c.199G>T) pathogenic?

CRIP3 p.Val67Leu (c.199G>T) is classified Uncertain significance in CRIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: ambiguous (0.4211); Very rare (popmax 0.00451%, eas).

How common is CRIP3 p.Val67Leu (c.199G>T) in the general population?

CRIP3 p.Val67Leu (c.199G>T) is very rare (popmax 0.00451%, eas) (gnomAD).

What do computational predictors say about CRIP3 p.Val67Leu (c.199G>T)?

AlphaMissense predicts ambiguous (score 0.4211) — an in-silico prediction, not a clinical call.

CRIP3 p.Val67Leu

c.199G>T · VCV4006846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4211 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00451%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4211	ambiguous
REVEL	0.698	pathogenic-leaning
SaProt	LLR -8.92	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,975 bp · p 0.92 · regional, not allelic
Overall
CADD	24.0	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 0.00451% East Asian · 2/44,358 alleles

Filtering AF 0.000747% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00028%

Overall 0.000563% 9/1,597,816 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00451%	22,179
Remaining individualsnot grpmax-eligible	0.00325%	30,798
South Asian	0.00222%	45,080
European (non-Finnish)	0.000257%	389,730

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.Val67Leu
Coding: c.199G>T
MANE Select: NM_206922
Type: single nucleotide variant
Location: chr6:43307741 (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-val67leu (accessed [today's date]).

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