Is CIMAP2 p.Pro69Arg (c.206C>G) pathogenic?

CIMAP2 p.Pro69Arg (c.206C>G) is classified Uncertain significance in CIMAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: ambiguous (0.5114); Very rare (popmax 0.00117%, sas).

How common is CIMAP2 p.Pro69Arg (c.206C>G) in the general population?

CIMAP2 p.Pro69Arg (c.206C>G) is very rare (popmax 0.00117%, sas) (gnomAD).

What do computational predictors say about CIMAP2 p.Pro69Arg (c.206C>G)?

AlphaMissense predicts ambiguous (score 0.5114) — an in-silico prediction, not a clinical call.

CIMAP2 p.Pro69Arg

c.206C>G · VCV3833513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00117%, sas)

Computational evidence

Protein change
AlphaMissense	0.5114	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -12.49	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 36 kb · p 0.61 · regional, not allelic
Overall
CADD	24.8	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 0.00117% South Asian · 1/85,738 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000381% 6/1,576,828 alleles · very rare exomes 6/1,424,478 · genomes 0/152,350 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00117%	85,738
European (non-Finnish)	0.00043%	232,318

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.Pro69Arg
Coding: c.206C>G
MANE Select: NM_001110533
Type: single nucleotide variant
Location: chr1:54807539 (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-pro69arg (accessed [today's date]).

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