Is CEMIP p.Ile478= (c.1434C>T) pathogenic?

CEMIP p.Ile478= (c.1434C>T) is classified Likely benign in CEMIP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-15). Ultra-rare (popmax 0.0117%, amr); Associated with CEMIP-related disorder.

What condition is associated with CEMIP p.Ile478= (c.1434C>T)?

CEMIP p.Ile478= (c.1434C>T) is associated with CEMIP-related disorder (ClinVar).

How common is CEMIP p.Ile478= (c.1434C>T) in the general population?

CEMIP p.Ile478= (c.1434C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

CEMIP p.Ile478=

c.1434C>T · rs202093898 · VCV3050640

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

CEMIP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -5.8
Overall
CADD	6.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,014 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00173% 28/1,613,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0048%	20,834
South Asian	0.00439%	22,761
East Asian	0.00223%	44,866
European (non-Finnish)	0.0011%	90,756

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: CEMIP
Protein: p.Ile478=
Coding: c.1434C>T
MANE Select: NM_001293298
dbSNP: rs202093898
Type: single nucleotide variant
Location: chr15:80906685 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69
Residue 478: the 'necessary for its endoplasmic reticulum (er) retention and interaction with hspa5' region

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

Disease context

CEMIP-related disorder

Similar variants

CEMIP c.241+8A>G Likely benign same condition
CEMIP p.Ala463Thr Likely benign ⚠ same condition
CEMIP p.Asp929= Benign same condition
CEMIP p.Ile194= Likely benign same condition
CEMIP p.Leu107= Likely benign same condition
CEMIP p.Leu1138= Likely benign same condition
CEMIP p.Pro1045= Likely benign same condition
CEMIP p.Pro556= Likely benign 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/cemip-p-ile478 (accessed [today's date]).

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