Is CIMAP2 p.Glu3Gln (c.7G>C) pathogenic?

CIMAP2 p.Glu3Gln (c.7G>C) is classified Uncertain significance in CIMAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely benign (0.1091); Very rare (popmax 8.72e-05%, nfe).

How common is CIMAP2 p.Glu3Gln (c.7G>C) in the general population?

CIMAP2 p.Glu3Gln (c.7G>C) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about CIMAP2 p.Glu3Gln (c.7G>C)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

CIMAP2 p.Glu3Gln

c.7G>C · VCV4653883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.76	GERP -3.2
Regional constraint	o/e 0.98	unconstrained · MANE · 36 kb · p 0.61 · regional, not allelic
Overall
CADD	3.969	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,560 alleles

Overall 0.000657% 1/152,250 alleles · very rare

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: CIMAP2
Protein: p.Glu3Gln
Coding: c.7G>C
MANE Select: NM_001110533
Type: single nucleotide variant
Location: chr1:54806123 (GRCh38)
Structure: AlphaFold pLDDT 64.45

Full CIMAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP2 p.Ala7Val Uncertain significance ★ ⚠ same type
CIMAP2 p.Ala8Thr Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg117Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg145Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg186Gln Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg203Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg232Cys Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg242Gln Uncertain significance ★ ⚠ 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/cimap2-p-glu3gln (accessed [today's date]).

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