Is CRIP2 p.Gln86His (c.258G>C) pathogenic?

CRIP2 p.Gln86His (c.258G>C) is classified Uncertain significance in CRIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.0888); Rare (popmax 0.319%, nfe).

How common is CRIP2 p.Gln86His (c.258G>C) in the general population?

CRIP2 p.Gln86His (c.258G>C) is rare (popmax 0.319%, nfe) (gnomAD).

What do computational predictors say about CRIP2 p.Gln86His (c.258G>C)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

CRIP2 p.Gln86His

c.258G>C · rs782271622 · VCV2291851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.319%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -1.5, phastCons 0.12
Regional constraint	o/e 1.29	unconstrained · MANE · 4,787 bp · p 4.9e-07 · regional, not allelic
Overall
CADD	11.83	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.319% European (non-Finnish) · 3,515/1,101,540 alleles

Filtering AF 0.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.307%

Overall 0.253% 3,633/1,434,282 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.319%	313
Remaining individualsnot grpmax-eligible	0.13%	767
African / African-American	0.0484%	2,064
Finnishnot grpmax-eligible	0.024%	4,174
Admixed American	0.00579%	17,258
South Asian	0.00148%	67,536

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: CRIP2
Protein: p.Gln86His
Coding: c.258G>C
MANE Select: NM_001312
dbSNP: rs782271622
Type: single nucleotide variant
Location: chr14:105478792 (GRCh38)
Gene constraint: LOEUF 1.553 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.78 · 1 PDB

Full CRIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRIP2 p.Ala113Val Uncertain significance ★ ⚠ same type
CRIP2 p.Ala166Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Ala82Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Ala96Gly Uncertain significance ★ ⚠ same type
CRIP2 p.Ala98Thr Uncertain significance ★ ⚠ same type
CRIP2 p.Arg128His Uncertain significance ★ ⚠ same type
CRIP2 p.Arg148Gly Uncertain significance ★ ⚠ same type
CRIP2 p.Arg148Trp 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/crip2-p-gln86his (accessed [today's date]).

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