Is CEMIP p.Gly840= (c.2520C>T) pathogenic?

CEMIP p.Gly840= (c.2520C>T) is classified Benign in CEMIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Rare (popmax 0.312%, nfe).

How common is CEMIP p.Gly840= (c.2520C>T) in the general population?

CEMIP p.Gly840= (c.2520C>T) is rare (popmax 0.312%, nfe) (gnomAD).

CEMIP p.Gly840=

c.2520C>T · rs76271429 · VCV714557

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.312%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.85	donor gain · deltas
Pangolin	Δ0.58	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -5.7	GERP -5.2
Overall
CADD	19.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.312% European (non-Finnish) · 3,683/1,180,028 alleles

Filtering AF 0.304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.3%

Overall 0.282% 4,556/1,614,162 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.29%	77
European (non-Finnish)grpmax	0.312%	320
Remaining individualsnot grpmax-eligible	0.286%	349
Admixed American	0.215%	465
South Asian	0.102%	979
Finnishnot grpmax-eligible	0.0625%	1,601
African / African-American	0.0573%	1,745
Middle Eastern	0.0495%	2,021
East Asian	0.00669%	14,957

Ashkenazi Jewish 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: CEMIP
Protein: p.Gly840=
Coding: c.2520C>T
MANE Select: NM_001293298
dbSNP: rs76271429
Type: single nucleotide variant
Location: chr15:80929082 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69

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

Similar variants

CEMIP p.Ala33Val Uncertain significance ★★ ⚠ same type
CEMIP p.Gly870Asp Uncertain significance ★★ ⚠ same type
CEMIP c.1086+82T>A Benign ★★ same type
CEMIP c.1087-239G>A Benign ★★ same type
CEMIP c.1412-76G>A Benign ★★ same type
CEMIP c.1587+57A>G Benign ★★ same type
CEMIP c.1587+79G>A Benign ★★ same type
CEMIP c.1797+102T>C Benign ★★ 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/cemip-p-gly840 (accessed [today's date]).

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