Is CMIP c.2091+5G>A pathogenic?

CMIP c.2091+5G>A is classified Benign in CMIP (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-11-12). Common (popmax 15%, eas) — too common for a highly-penetrant pathogenic allele; Associated with CMIP-related disorder.

What condition is associated with CMIP c.2091+5G>A?

CMIP c.2091+5G>A is associated with CMIP-related disorder (ClinVar).

CMIP c.2091+5G>A

Q: How common is CMIP c.2091+5G>A in the general population?

CMIP c.2091+5G>A is common (popmax 15%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs72831128 · VCV3055438

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 15%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

CMIP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -1.6
Overall
CADD	0.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15% East Asian · 6,673/44,378 alleles

Filtering AF 14.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 8.49% 135,826/1,600,218 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	15%	7
Finnishnot grpmax-eligible	10.9%	9
European (non-Finnish)	8.74%	11
Remaining individualsnot grpmax-eligible	8.51%	12
Middle Eastern	7.57%	13
Admixed American	6.57%	15
Ashkenazi Jewishnot grpmax-eligible	6.47%	15
South Asian	5.28%	19
African / African-American	5.04%	20
Amishnot grpmax-eligible	4.4%	23

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: CMIP
Coding: c.2091+5G>A
MANE Select: NM_198390
dbSNP: rs72831128
Type: single nucleotide variant
Location: chr16:81704090 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.52

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

Disease context

CMIP-related disorder

Similar variants

CMIP p.Ala92Thr Uncertain significance ★ ⚠ same condition
CMIP p.Arg149Ter Uncertain significance ★ same condition
CMIP p.Glu495Lys Uncertain significance ⚠ same condition
CMIP p.Ile199Val Uncertain significance ⚠ same condition
CMIP c.1896+8C>T Likely benign same condition
CMIP c.2091+4C>T Likely benign same condition
CMIP p.Arg253= Likely benign same condition
CMIP p.Arg282= 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/cmip-c-2091-plus-5g-a (accessed [today's date]).

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