Is CIT p.Asn786Asp (c.2356A>G) pathogenic?

CIT p.Asn786Asp (c.2356A>G) is classified Uncertain significance in CIT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely benign (0.1201); Very rare (popmax 0.00127%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CIT p.Asn786Asp (c.2356A>G)?

CIT p.Asn786Asp (c.2356A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CIT p.Asn786Asp (c.2356A>G) in the general population?

CIT p.Asn786Asp (c.2356A>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about CIT p.Asn786Asp (c.2356A>G)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

CIT p.Asn786Asp

c.2356A>G · rs146931583 · VCV3145146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.25	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 55 kb · p 2.1e-24 · regional, not allelic
Overall
CADD	22.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N744D vs ClinVar N786D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,180,024 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00109% 16/1,461,870 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)grpmax	0.00127%	78,668

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn786Asp
Coding: c.2356A>G
MANE Select: NM_001206999
dbSNP: rs146931583
Type: single nucleotide variant
Location: chr12:119761004 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT p.Asn786Ser Uncertain significance ★★ ⚠ same residue
CIT p.Arg1178Ter Pathogenic ★★ same condition
CIT c.4168+5G>A Uncertain significance ★★ same condition
CIT p.Ala1527Val Uncertain significance ★★ ⚠ same condition
CIT p.Ala495Ser Uncertain significance ★★ ⚠ same condition
CIT p.Ala8Val Uncertain significance ★★ ⚠ same condition
CIT p.Arg100Gly Uncertain significance ★★ ⚠ same condition
CIT p.Arg1469Cys Uncertain significance ★★ ⚠ 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-asn786asp (accessed [today's date]).

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