Is CRIPT p.Ser70Phe (c.209C>T) pathogenic?

CRIPT p.Ser70Phe (c.209C>T) is classified Uncertain significance in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely pathogenic (0.8392); Very rare (popmax 0.00224%, eas); Associated with Inborn genetic diseases.

What condition is associated with CRIPT p.Ser70Phe (c.209C>T)?

CRIPT p.Ser70Phe (c.209C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CRIPT p.Ser70Phe (c.209C>T) in the general population?

CRIPT p.Ser70Phe (c.209C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about CRIPT p.Ser70Phe (c.209C>T)?

AlphaMissense predicts likely pathogenic (score 0.8392) — an in-silico prediction, not a clinical call.

CRIPT p.Ser70Phe

c.209C>T · VCV4616582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8392 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8392	likely pathogenic
REVEL	0.701	pathogenic-leaning
SaProt	LLR -10.16	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 6,941 bp · p 0.1 · regional, not allelic
Overall
CADD	28.8	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 0.00224% East Asian · 1/44,664 alleles

Overall 6.86e-05% 1/1,458,660 alleles · very rare

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.Ser70Phe
Coding: c.209C>T
MANE Select: NM_014171
Type: single nucleotide variant
Location: chr2:46623835 (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-ser70phe (accessed [today's date]).

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