Is CIMAP2 p.Arg370Pro (c.1109G>C) pathogenic?

CIMAP2 p.Arg370Pro (c.1109G>C) is classified Uncertain significance in CIMAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely pathogenic (0.6059); Very rare (popmax 0.00167%, amr).

How common is CIMAP2 p.Arg370Pro (c.1109G>C) in the general population?

CIMAP2 p.Arg370Pro (c.1109G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CIMAP2 p.Arg370Pro (c.1109G>C)?

AlphaMissense predicts likely pathogenic (score 0.6059) — an in-silico prediction, not a clinical call.

CIMAP2 p.Arg370Pro

c.1109G>C · VCV3267405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6059 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6059	likely pathogenic · top 10% in CIMAP2
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.45, phastCons 0.8
Regional constraint	o/e 0.98	unconstrained · MANE · 36 kb · p 0.61 · regional, not allelic
Overall
CADD	22.3	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 0.00167% Admixed American · 1/60,024 alleles

Overall 0.000137% 2/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,024
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Arg370Pro
Coding: c.1109G>C
MANE Select: NM_001110533
Type: single nucleotide variant
Location: chr1:54817047 (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-arg370pro (accessed [today's date]).

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