Is CIMAP1A p.Arg14His (c.41G>A) pathogenic?

CIMAP1A p.Arg14His (c.41G>A) is classified Uncertain significance in CIMAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely benign (0.1454); Ultra-rare (popmax 0.0241%, amr).

How common is CIMAP1A p.Arg14His (c.41G>A) in the general population?

CIMAP1A p.Arg14His (c.41G>A) is ultra-rare (popmax 0.0241%, amr) (gnomAD).

What do computational predictors say about CIMAP1A p.Arg14His (c.41G>A)?

AlphaMissense predicts likely benign (score 0.1454) — an in-silico prediction, not a clinical call.

CIMAP1A p.Arg14His

c.41G>A · rs375670921 · VCV3235343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1454 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1454	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -9.95	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 9.4	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,725 bp · p 0.21 · regional, not allelic
Overall
CADD	25.3	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 0.0241% Admixed American · 14/57,994 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.00226% 36/1,594,192 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0241%	4,142
South Asian	0.00566%	17,672
Remaining individualsnot grpmax-eligible	0.00487%	20,533
East Asian	0.00457%	21,887
African / African-American	0.00403%	24,785
European (non-Finnish)	0.000769%	129,981

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.Arg14His
Coding: c.41G>A
MANE Select: NM_053280
dbSNP: rs375670921
Type: single nucleotide variant
Location: chr11:197345 (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.Arg166His Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg186Cys Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg191Trp Uncertain significance ★ ⚠ same type
CIMAP1A p.Arg205Pro 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-arg14his (accessed [today's date]).

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