Is CIMAP1A p.Glu3Lys (c.7G>A) pathogenic?

CIMAP1A p.Glu3Lys (c.7G>A) is classified Uncertain significance in CIMAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1257); Very rare (popmax 0.00406%, afr).

How common is CIMAP1A p.Glu3Lys (c.7G>A) in the general population?

CIMAP1A p.Glu3Lys (c.7G>A) is very rare (popmax 0.00406%, afr) (gnomAD).

What do computational predictors say about CIMAP1A p.Glu3Lys (c.7G>A)?

AlphaMissense predicts likely benign (score 0.1257) — an in-silico prediction, not a clinical call.

CIMAP1A p.Glu3Lys

c.7G>A · VCV4229030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1257 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00406%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1257	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -8.99	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 8.2	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,725 bp · p 0.21 · regional, not allelic
Overall
CADD	22.6	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 0.00406% African / African-American · 3/73,952 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000499%

Overall 0.000254% 4/1,577,708 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00406%	24,651
European (non-Finnish)	8.62e-05%	1,160,630

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.Glu3Lys
Coding: c.7G>A
MANE Select: NM_053280
Type: single nucleotide variant
Location: chr11:197311 (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.Arg205Pro 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-glu3lys (accessed [today's date]).

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