Is CEMIP p.Lys158= (c.474G>A) pathogenic?

CEMIP p.Lys158= (c.474G>A) is classified Benign in CEMIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.6%, nfe).

How common is CEMIP p.Lys158= (c.474G>A) in the general population?

CEMIP p.Lys158= (c.474G>A) is rare (popmax 0.6%, nfe) (gnomAD).

CEMIP p.Lys158=

c.474G>A · rs72740115 · VCV770434

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.6%, nfe)

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 2.1	GERP -1.6, phastCons 1
Overall
CADD	6.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.6% European (non-Finnish) · 7,083/1,180,026 alleles

Filtering AF 0.589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.584%

Overall 0.492% 7,936/1,614,210 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.776%	129
European (non-Finnish)grpmax	0.6%	167
Remaining individualsnot grpmax-eligible	0.322%	311
Amishnot grpmax-eligible	0.11%	912
Admixed American	0.0966%	1,035
African / African-American	0.0893%	1,120
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,184
South Asian	0.00439%	22,772

Finnish 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.Lys158=
Coding: c.474G>A
MANE Select: NM_001293298
dbSNP: rs72740115
Type: single nucleotide variant
Location: chr15:80880993 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.69
Residue 158: the g8 domain

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-lys158 (accessed [today's date]).

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