Is CIMAP1B p.Pro33Gln (c.98C>A) pathogenic?

CIMAP1B p.Pro33Gln (c.98C>A) is classified Uncertain significance in CIMAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: ambiguous (0.3439); Very rare (popmax 0.00378%, amr).

How common is CIMAP1B p.Pro33Gln (c.98C>A) in the general population?

CIMAP1B p.Pro33Gln (c.98C>A) is very rare (popmax 0.00378%, amr) (gnomAD).

What do computational predictors say about CIMAP1B p.Pro33Gln (c.98C>A)?

AlphaMissense predicts ambiguous (score 0.3439) — an in-silico prediction, not a clinical call.

CIMAP1B p.Pro33Gln

c.98C>A · rs540657372 · VCV2319931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00378%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3439	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 1,594 bp · p 0.18 · regional, not allelic
Overall
CADD	28.1	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 0.00378% Admixed American · 1/26,484 alleles

Filtering AF 0.000208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000669% 9/1,345,544 alleles · very rare exomes 9/1,193,282 · genomes 0/152,262 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00378%	26,484
Remaining individualsnot grpmax-eligible	0.002%	49,916
Finnishnot grpmax-eligible	0.00191%	52,470
European (non-Finnish)	0.000577%	173,326

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: CIMAP1B
Protein: p.Pro33Gln
Coding: c.98C>A
MANE Select: NM_001014440
dbSNP: rs540657372
Type: single nucleotide variant
Location: chr22:50531980 (GRCh38)
Structure: AlphaFold pLDDT 73.82

Full CIMAP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1B p.Ala134Glu Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala134Val Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala143Val Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala245Thr Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala39Thr Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala84Ser Uncertain significance ★ ⚠ same type
CIMAP1B p.Ala97Val Uncertain significance ★ ⚠ same type
CIMAP1B p.Arg16Cys 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/cimap1b-p-pro33gln (accessed [today's date]).

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