Is CIMIP2A p.Pro185Ser (c.553C>T) pathogenic?

CIMIP2A p.Pro185Ser (c.553C>T) is classified Uncertain significance in CIMIP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). AlphaMissense: likely benign (0.0762); Very rare (popmax 0.00275%, sas).

How common is CIMIP2A p.Pro185Ser (c.553C>T) in the general population?

CIMIP2A p.Pro185Ser (c.553C>T) is very rare (popmax 0.00275%, sas) (gnomAD).

What do computational predictors say about CIMIP2A p.Pro185Ser (c.553C>T)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

CIMIP2A p.Pro185Ser

c.553C>T · rs1157982075 · VCV2399189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00275%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.14	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 0.29	GERP -3.1
Regional constraint	o/e 1.43	unconstrained · MANE · 4,012 bp · p 1.9e-18 · regional, not allelic
Overall
CADD	2.254	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 0.00275% South Asian · 2/72,826 alleles

Filtering AF 0.000456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000171%

Overall 0.000689% 6/870,918 alleles · very rare exomes 6/721,564 · genomes 0/149,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00275%	36,413
Admixed American	0.00207%	48,202
European (non-Finnish)	0.000571%	175,072

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: CIMIP2A
Protein: p.Pro185Ser
Coding: c.553C>T
MANE Select: NM_001001710
dbSNP: rs1157982075
Type: single nucleotide variant
Location: chr9:137245188 (GRCh38)
Structure: AlphaFold pLDDT 61.88

Full CIMIP2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMIP2A p.Pro185Leu Uncertain significance ★ ⚠ same residue
STPG3 p.Ser126Gly Benign ★★ same type
CIMIP2A p.Ala187Pro Uncertain significance ★ ⚠ same type
CIMIP2A p.Ala215Val Uncertain significance ★ ⚠ same type
CIMIP2A p.Ala241Val Uncertain significance ★ ⚠ same type
CIMIP2A p.Ala311Thr Uncertain significance ★ ⚠ same type
CIMIP2A p.Arg188Cys Uncertain significance ★ ⚠ same type
CIMIP2A p.Arg189Cys 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/cimip2a-p-pro185ser (accessed [today's date]).

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