Is CRIP1 p.Ala58Pro (c.172G>C) pathogenic?

CRIP1 p.Ala58Pro (c.172G>C) is classified Uncertain significance in CRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.8602); Ultra-rare (popmax 0.0334%, eas).

How common is CRIP1 p.Ala58Pro (c.172G>C) in the general population?

CRIP1 p.Ala58Pro (c.172G>C) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about CRIP1 p.Ala58Pro (c.172G>C)?

AlphaMissense predicts likely pathogenic (score 0.8602) — an in-silico prediction, not a clinical call.

CRIP1 p.Ala58Pro

c.172G>C · VCV4234165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8602 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8602	likely pathogenic
REVEL	0.391	indeterminate
SaProt	LLR -13.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP -3.4, phastCons 0.1
Regional constraint	o/e 1.20	unconstrained · MANE · 1,248 bp · p 0.039 · regional, not allelic
Overall
CADD	7.778	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,890 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.0103% 166/1,613,300 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,993
European (non-Finnish)	0.0122%	8,194
Remaining individualsnot grpmax-eligible	0.008%	12,494
Admixed American	0.00333%	29,999

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.Ala58Pro
Coding: c.172G>C
MANE Select: NM_001311
Type: single nucleotide variant
Location: chr14:105488367 (GRCh38)
Gene constraint: LOEUF 1.447 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.41
Residue 58: the lim zinc-binding domain

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

Similar variants

CRIP1 p.Cys52Phe Benign ★★ 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
CRIP1 p.Arg68Pro Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Trp 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-ala58pro (accessed [today's date]).

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