Is CIMAP2 p.Pro329Arg (c.986C>G) pathogenic?

CIMAP2 p.Pro329Arg (c.986C>G) is classified Uncertain significance in CIMAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely benign (0.2423); Ultra-rare (popmax 0.0165%, mid).

How common is CIMAP2 p.Pro329Arg (c.986C>G) in the general population?

CIMAP2 p.Pro329Arg (c.986C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CIMAP2 p.Pro329Arg (c.986C>G)?

AlphaMissense predicts likely benign (score 0.2423) — an in-silico prediction, not a clinical call.

CIMAP2 p.Pro329Arg

c.986C>G · VCV3833514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2423 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2423	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 36 kb · p 0.61 · regional, not allelic
Overall
CADD	21.5	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000821% 12/1,461,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
South Asian	0.00549%	18,215
European (non-Finnish)	0.000508%	196,668

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.Pro329Arg
Coding: c.986C>G
MANE Select: NM_001110533
Type: single nucleotide variant
Location: chr1:54814975 (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-pro329arg (accessed [today's date]).

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