Is CRIPT c.83-1G>A pathogenic?

CRIPT c.83-1G>A is classified Likely pathogenic in CRIPT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-03). Very rare (popmax 0.00315%, nfe); Associated with Fetal anomalies with a likely genetic cause.

What condition is associated with CRIPT c.83-1G>A?

CRIPT c.83-1G>A is associated with Fetal anomalies with a likely genetic cause (ClinVar).

How common is CRIPT c.83-1G>A in the general population?

CRIPT c.83-1G>A is very rare (popmax 0.00315%, nfe) (gnomAD).

CRIPT c.83-1G>A

rs746415991 · VCV2150415

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00315%, nfe)

Conditions

Fetal anomalies with a likely genetic cause

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	acceptor -1	canonical splice dinucleotide (acceptor -1) · inside the BP7-excluded zone
SpliceAI	Δ1.00	acceptor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.90	loss · gain 0.24 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Non-coding constraint	Z 1.14	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00315% European (non-Finnish) · 37/1,175,090 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00203%

Overall 0.00243% 39/1,607,078 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00322%	31,095
European (non-Finnish)grpmax	0.00315%	31,759

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CRIPT
Coding: c.83-1G>A
MANE Select: NM_014171
dbSNP: rs746415991
Type: single nucleotide variant
Location: chr2:46619626 (GRCh38)
Gene constraint: LOEUF 1.852 · pLI 0.19 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB

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

Disease context

Fetal anomalies with a likely genetic cause

Similar variants

CRIPT p.Asp92Gly Uncertain significance ★ same condition
CRIPT p.Lys5Glu Likely benign same condition
CRIPT p.Ala45Pro Uncertain significance ★★ ⚠ same type
CRIPT p.Ala84Val Uncertain significance ★★ ⚠ same type
CRIPT p.Cys86Phe Uncertain significance ★★ ⚠ same type
CRIPT p.Gln74Arg Uncertain significance ★★ ⚠ same type
CRIPT p.Gly81Val Uncertain significance ★★ ⚠ same type
CRIPT p.Lys88Arg 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/cript-c-83-minus-1g-a (accessed [today's date]).

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