Is CIMAP3 p.Pro140Ser (c.418C>T) pathogenic?

CIMAP3 p.Pro140Ser (c.418C>T) is classified Uncertain significance in CIMAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.1008); Very rare (popmax 0.00017%, nfe).

How common is CIMAP3 p.Pro140Ser (c.418C>T) in the general population?

CIMAP3 p.Pro140Ser (c.418C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CIMAP3 p.Pro140Ser (c.418C>T)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

CIMAP3 p.Pro140Ser

c.418C>T · VCV4003080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -1.91	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	GERP -0.29
Regional constraint	o/e 0.95	unconstrained · MANE · 4,671 bp · p 0.46 · regional, not allelic
Overall
CADD	2.683	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 0.00017% European (non-Finnish) · 2/1,179,888 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,724 alleles · very rare

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: CIMAP3
Protein: p.Pro140Ser
Coding: c.418C>T
MANE Select: NM_181643
Type: single nucleotide variant
Location: chr1:111350134 (GRCh38)
Structure: AlphaFold pLDDT 72.99

Full CIMAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP3 p.Ala110Val Uncertain significance ★ ⚠ same type
CIMAP3 p.Ala145Gly Uncertain significance ★ ⚠ same type
CIMAP3 p.Arg182Cys Uncertain significance ★ ⚠ same type
CIMAP3 p.Arg182His Uncertain significance ★ ⚠ same type
CIMAP3 p.Arg94Lys Uncertain significance ★ ⚠ same type
CIMAP3 p.Asn181Asp Uncertain significance ★ ⚠ same type
CIMAP3 p.Gln162Arg Uncertain significance ★ ⚠ same type
CIMAP3 p.Gly33Arg 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/cimap3-p-pro140ser (accessed [today's date]).

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