Is CRIP3 p.Arg50Trp (c.148A>T) pathogenic?

CRIP3 p.Arg50Trp (c.148A>T) is classified Uncertain significance in CRIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-10). AlphaMissense: likely benign (0.1178); Very rare (popmax 0.00333%, amr).

How common is CRIP3 p.Arg50Trp (c.148A>T) in the general population?

CRIP3 p.Arg50Trp (c.148A>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CRIP3 p.Arg50Trp (c.148A>T)?

AlphaMissense predicts likely benign (score 0.1178) — an in-silico prediction, not a clinical call.

CRIP3 p.Arg50Trp

c.148A>T · VCV3497092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1178 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1178	likely benign
REVEL	0.525	indeterminate
SaProt	LLR -11.17	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,975 bp · p 0.92 · regional, not allelic
Overall
CADD	27.9	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 0.00333% Admixed American · 2/59,988 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00131% 2/152,134 alleles · very rare

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.Arg50Trp
Coding: c.148A>T
MANE Select: NM_206922
Type: single nucleotide variant
Location: chr6:43307887 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 50: 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.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
CRIP3 p.Gly161Glu 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-arg50trp (accessed [today's date]).

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