Is CPE p.Thr313Ile (c.938C>T) pathogenic?

CPE p.Thr313Ile (c.938C>T) is classified Uncertain significance in CPE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely benign (0.1018); Ultra-rare (popmax 0.02%, afr); Associated with CPE-related disorder.

What condition is associated with CPE p.Thr313Ile (c.938C>T)?

CPE p.Thr313Ile (c.938C>T) is associated with CPE-related disorder (ClinVar).

How common is CPE p.Thr313Ile (c.938C>T) in the general population?

CPE p.Thr313Ile (c.938C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about CPE p.Thr313Ile (c.938C>T)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

CPE p.Thr313Ile

c.938C>T · rs150784271 · VCV2632387

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CPE-related disorder

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -1.88	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 118 kb · p 0.00025 · regional, not allelic
Overall
CADD	18.57	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 0.02% African / African-American · 15/75,050 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00987%

Overall 0.00112% 18/1,614,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,003
Middle Eastern	0.0165%	6,062
Admixed American	0.00167%	60,020
South Asian	0.0011%	91,074

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: CPE
Protein: p.Thr313Ile
Coding: c.938C>T
MANE Select: NM_001873
dbSNP: rs150784271
Type: single nucleotide variant
Location: chr4:165484569 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83
Residue 313: a UniProt-annotated variant site (in bdvs); the peptidase m14 domain

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

Disease context

CPE-related disorder

Similar variants

CPE p.Arg121Ter Pathogenic ★★ same condition
CPE c.974-3C>T Uncertain significance ★ same condition
CPE p.Ile415Met Uncertain significance ★ ⚠ same condition
CPE p.Pro30Ala Uncertain significance ★ ⚠ same condition
CPE c.673-2A>G Uncertain significance same condition
CPE p.Ala231Gly Uncertain significance ⚠ same condition
CPE p.Ala266Ser Uncertain significance ⚠ same condition
CPE p.Ala389Val 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/cpe-p-thr313ile (accessed [today's date]).

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