Is CIMAP1A p.Arg205Pro (c.614G>C) pathogenic?

CIMAP1A p.Arg205Pro (c.614G>C) is classified Uncertain significance in CIMAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.9094); Ultra-rare (popmax 0.0852%, eas).

How common is CIMAP1A p.Arg205Pro (c.614G>C) in the general population?

CIMAP1A p.Arg205Pro (c.614G>C) is ultra-rare (popmax 0.0852%, eas) (gnomAD).

What do computational predictors say about CIMAP1A p.Arg205Pro (c.614G>C)?

AlphaMissense predicts likely pathogenic (score 0.9094) — an in-silico prediction, not a clinical call.

CIMAP1A p.Arg205Pro

c.614G>C · VCV4229023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9094 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0852%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9094	likely pathogenic · top 9% in CIMAP1A
REVEL	0.318	indeterminate
SaProt	LLR -12.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,725 bp · p 0.21 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0852% East Asian · 36/42,266 alleles

Filtering AF 0.0632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0556%

Overall 0.00255% 40/1,566,238 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0852%	1,174
Remaining individualsnot grpmax-eligible	0.00165%	60,692
South Asian	0.00117%	85,268
European (non-Finnish)	0.000173%	577,591

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: CIMAP1A
Protein: p.Arg205Pro
Coding: c.614G>C
MANE Select: NM_053280
Type: single nucleotide variant
Location: chr11:199448 (GRCh38)
Structure: AlphaFold pLDDT 74.04

Full CIMAP1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1A p.Ala156Thr Uncertain significance ★ ⚠ same type
CIMAP1A p.Ala203Asp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg127Trp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg14His Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg166His Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg186Cys Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg191Trp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg47His 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/cimap1a-p-arg205pro (accessed [today's date]).

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