Is CRIP1 p.Pro55His (c.164C>A) pathogenic?

CRIP1 p.Pro55His (c.164C>A) is classified Uncertain significance in CRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely pathogenic (0.7686); Ultra-rare (popmax 0.0165%, mid).

How common is CRIP1 p.Pro55His (c.164C>A) in the general population?

CRIP1 p.Pro55His (c.164C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CRIP1 p.Pro55His (c.164C>A)?

AlphaMissense predicts likely pathogenic (score 0.7686) — an in-silico prediction, not a clinical call.

CRIP1 p.Pro55His

c.164C>A · VCV3269513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7686	likely pathogenic
REVEL	0.588	indeterminate
SaProt	LLR -15.03	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 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 1,248 bp · p 0.039 · regional, not allelic
Overall
CADD	25.5	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 0.0165% Middle Eastern · 1/6,050 alleles

Filtering AF 0.00969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00843% 136/1,613,382 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,050
European (non-Finnish)	0.0113%	8,872
Remaining individualsnot grpmax-eligible	0.0032%	31,236

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.Pro55His
Coding: c.164C>A
MANE Select: NM_001311
Type: single nucleotide variant
Location: chr14:105488359 (GRCh38)
Gene constraint: LOEUF 1.447 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.41
Residue 55: the lim zinc-binding domain

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

Similar variants

CRIP1 p.Pro55Ala 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-pro55his (accessed [today's date]).

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