Is CRIPT p.His71Arg (c.212A>G) pathogenic?

CRIPT p.His71Arg (c.212A>G) is classified Uncertain significance in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely pathogenic (0.599); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with CRIPT p.His71Arg (c.212A>G)?

CRIPT p.His71Arg (c.212A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CRIPT p.His71Arg (c.212A>G) in the general population?

CRIPT p.His71Arg (c.212A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CRIPT p.His71Arg (c.212A>G)?

AlphaMissense predicts likely pathogenic (score 0.599) — an in-silico prediction, not a clinical call.

CRIPT p.His71Arg

c.212A>G · VCV3497127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.599 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.599	likely pathogenic
REVEL	0.678	pathogenic-leaning
SaProt	LLR -14.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 6,941 bp · p 0.1 · regional, not allelic
Overall
CADD	26.0	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 0.00134% African / African-American · 1/74,846 alleles

Overall 0.000137% 2/1,454,704 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,216
African / African-Americangrpmax	0.00134%	74,846

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
Protein: p.His71Arg
Coding: c.212A>G
MANE Select: NM_014171
Type: single nucleotide variant
Location: chr2:46623838 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRIPT p.Ala45Pro Uncertain significance ★★ ⚠ same condition
CRIPT p.Ala84Val Uncertain significance ★★ ⚠ same condition
CRIPT p.Cys86Phe Uncertain significance ★★ ⚠ same condition
CRIPT p.Gln74Arg Uncertain significance ★★ ⚠ same condition
CRIPT p.Gly81Val Uncertain significance ★★ ⚠ same condition
CRIPT p.Lys88Arg Uncertain significance ★★ ⚠ same condition
CRIPT p.Ser64Phe Uncertain significance ★★ ⚠ same condition
CRIPT p.Ala39Val Uncertain significance ★ ⚠ same condition

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-p-his71arg (accessed [today's date]).

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