Is CRIP1 p.Glu47Lys (c.139G>A) pathogenic?

CRIP1 p.Glu47Lys (c.139G>A) is classified Uncertain significance in CRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: ambiguous (0.4061); Very rare (popmax 0.00373%, nfe).

How common is CRIP1 p.Glu47Lys (c.139G>A) in the general population?

CRIP1 p.Glu47Lys (c.139G>A) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about CRIP1 p.Glu47Lys (c.139G>A)?

AlphaMissense predicts ambiguous (score 0.4061) — an in-silico prediction, not a clinical call.

CRIP1 p.Glu47Lys

c.139G>A · rs369446226 · VCV3077448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4061 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4061	ambiguous
REVEL	0.276	benign-leaning
SaProt	LLR -7.09	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 1,248 bp · p 0.039 · regional, not allelic
Overall
CADD	26.6	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 0.00373% European (non-Finnish) · 44/1,180,014 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00328% 53/1,613,408 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)grpmax	0.00373%	26,818
Admixed American	0.00333%	29,999
Finnishnot grpmax-eligible	0.00315%	31,700
East Asian	0.00223%	44,888

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: CRIP1
Protein: p.Glu47Lys
Coding: c.139G>A
MANE Select: NM_001311
dbSNP: rs369446226
Type: single nucleotide variant
Location: chr14:105488334 (GRCh38)
Gene constraint: LOEUF 1.447 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.41
Residue 47: the lim zinc-binding domain

Full CRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRIP1 p.Glu47Gln Uncertain significance ★ ⚠ same residue
CRIP1 p.Cys52Phe Benign ★★ same type
CRIP1 p.Ala58Pro Uncertain significance ★ ⚠ same type
CRIP1 p.Arg16Thr Uncertain significance ★ ⚠ same type
CRIP1 p.Arg26Gln Uncertain significance ★ ⚠ same type
CRIP1 p.Arg26Trp Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Gln Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Gly 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/crip1-p-glu47lys (accessed [today's date]).

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