Is CRIP3 p.Ser40Tyr (c.119C>A) pathogenic?

CRIP3 p.Ser40Tyr (c.119C>A) is classified Uncertain significance in CRIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.2187); Ultra-rare (popmax 0.029%, eas).

How common is CRIP3 p.Ser40Tyr (c.119C>A) in the general population?

CRIP3 p.Ser40Tyr (c.119C>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about CRIP3 p.Ser40Tyr (c.119C>A)?

AlphaMissense predicts likely benign (score 0.2187) — an in-silico prediction, not a clinical call.

CRIP3 p.Ser40Tyr

c.119C>A · rs776090364 · VCV2391349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2187 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2187	likely benign
REVEL	0.747	pathogenic-leaning
SaProt	LLR -11.47	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,975 bp · p 0.92 · regional, not allelic
Overall
CADD	29.2	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 0.029% East Asian · 13/44,832 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00093% 15/1,612,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,449
Remaining individualsnot grpmax-eligible	0.0016%	62,468
South Asian	0.0011%	90,866

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.Ser40Tyr
Coding: c.119C>A
MANE Select: NM_206922
dbSNP: rs776090364
Type: single nucleotide variant
Location: chr6:43308334 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 40: the lim zinc-binding 1 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-ser40tyr (accessed [today's date]).

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