Is CIT p.Pro1871= (c.5613T>G) pathogenic?

CIT p.Pro1871= (c.5613T>G) is classified Likely benign in CIT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-19). Very rare (popmax 0.000179%, nfe); Associated with CIT-related disorder.

What condition is associated with CIT p.Pro1871= (c.5613T>G)?

CIT p.Pro1871= (c.5613T>G) is associated with CIT-related disorder (ClinVar).

How common is CIT p.Pro1871= (c.5613T>G) in the general population?

CIT p.Pro1871= (c.5613T>G) is very rare (popmax 0.000179%, nfe) (gnomAD).

CIT p.Pro1871=

c.5613T>G · rs2136979223 · VCV3039941

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000179%, nfe)

Conditions

CIT-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.161	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.68, phastCons 0.99
Overall
CADD	14.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000179% European (non-Finnish) · 2/1,116,462 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000145% 2/1,377,366 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: CIT
Protein: p.Pro1871=
Coding: c.5613T>G
MANE Select: NM_001206999
dbSNP: rs2136979223
Type: single nucleotide variant
Location: chr12:119700755 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 1871: the cnh domain

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

Disease context

CIT-related disorder

Similar variants

CIT p.Gln64Ter Likely pathogenic ★ same condition
CIT c.2532-9C>T Likely benign same condition
CIT c.3486+7G>A Likely benign same condition
CIT c.6187-4C>T Likely benign same condition
CIT p.Asn1972= Likely benign same condition
CIT p.Ile1356= Likely benign same condition
CIT p.Leu1803= Likely benign same condition
CIT p.Pro1377= Likely benign same condition

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/cit-p-pro1871 (accessed [today's date]).

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