Is CIMAP2 p.Pro28Leu (c.83C>T) pathogenic?

CIMAP2 p.Pro28Leu (c.83C>T) is classified Uncertain significance in CIMAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: ambiguous (0.4164); Very rare (popmax 0.0024%, sas).

How common is CIMAP2 p.Pro28Leu (c.83C>T) in the general population?

CIMAP2 p.Pro28Leu (c.83C>T) is very rare (popmax 0.0024%, sas) (gnomAD).

What do computational predictors say about CIMAP2 p.Pro28Leu (c.83C>T)?

AlphaMissense predicts ambiguous (score 0.4164) — an in-silico prediction, not a clinical call.

CIMAP2 p.Pro28Leu

c.83C>T · VCV3833517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0024%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4164	ambiguous
REVEL	0.29	benign-leaning
SaProt	LLR -8.89	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.63, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 36 kb · p 0.61 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0024% South Asian · 2/83,434 alleles

Filtering AF 0.000398% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000149%

Overall 0.000287% 4/1,392,108 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0024%	41,717
Finnishnot grpmax-eligible	0.00185%	54,042
European (non-Finnish)	8.7e-05%	1,149,623

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: CIMAP2
Protein: p.Pro28Leu
Coding: c.83C>T
MANE Select: NM_001110533
Type: single nucleotide variant
Location: chr1:54806199 (GRCh38)
Structure: AlphaFold pLDDT 64.45

Full CIMAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP2 p.Ala7Val Uncertain significance ★ ⚠ same type
CIMAP2 p.Ala8Thr Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg117Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg145Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg186Gln Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg203Trp Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg232Cys Uncertain significance ★ ⚠ same type
CIMAP2 p.Arg242Gln 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/cimap2-p-pro28leu (accessed [today's date]).

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