Is CIMAP1A p.Arg186Cys (c.556C>T) pathogenic?

CIMAP1A p.Arg186Cys (c.556C>T) is classified Uncertain significance in CIMAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-22). AlphaMissense: likely benign (0.1066); Very rare (popmax 0.00474%, nfe).

How common is CIMAP1A p.Arg186Cys (c.556C>T) in the general population?

CIMAP1A p.Arg186Cys (c.556C>T) is very rare (popmax 0.00474%, nfe) (gnomAD).

What do computational predictors say about CIMAP1A p.Arg186Cys (c.556C>T)?

AlphaMissense predicts likely benign (score 0.1066) — an in-silico prediction, not a clinical call.

CIMAP1A p.Arg186Cys

c.556C>T · VCV4003052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00474%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1066	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -5.67	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 4.6	phastCons 0.99
Regional constraint	o/e 1.07	unconstrained · MANE · 2,725 bp · p 0.21 · regional, not allelic
Overall
CADD	22.4	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 0.00474% European (non-Finnish) · 55/1,159,622 alleles

Filtering AF 0.00373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00335%

Overall 0.00381% 60/1,574,722 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00474%	21,084
East Asian	0.00466%	21,480
Remaining individualsnot grpmax-eligible	0.00328%	30,496
South Asian	0.00116%	85,902

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.Arg186Cys
Coding: c.556C>T
MANE Select: NM_053280
Type: single nucleotide variant
Location: chr11:199390 (GRCh38)
Structure: AlphaFold pLDDT 74.04

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

Similar variants

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CIMAP1A p.Arg127Trp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg14His Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg166His Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg191Trp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg205Pro Uncertain significance ★ ⚠ same type
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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-arg186cys (accessed [today's date]).

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