Is CEMIP p.Glu841Lys (c.2521G>A) pathogenic?

CEMIP p.Glu841Lys (c.2521G>A) is classified Uncertain significance in CEMIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely pathogenic (0.9578); Very rare (popmax 0.0022%, sas).

How common is CEMIP p.Glu841Lys (c.2521G>A) in the general population?

CEMIP p.Glu841Lys (c.2521G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CEMIP p.Glu841Lys (c.2521G>A)?

AlphaMissense predicts likely pathogenic (score 0.9578) — an in-silico prediction, not a clinical call.

CEMIP p.Glu841Lys

c.2521G>A · VCV3831446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9578 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9578	likely pathogenic
REVEL	0.693	pathogenic-leaning
SaProt	LLR -4.77	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 6e-09 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.0013% 19/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,542
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.00136%	73,753

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.Glu841Lys
Coding: c.2521G>A
MANE Select: NM_001293298
Type: single nucleotide variant
Location: chr15:80929083 (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-glu841lys (accessed [today's date]).

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