Is CIT p.Asn786Ser (c.2357A>G) pathogenic?

CIT p.Asn786Ser (c.2357A>G) is classified Uncertain significance in CIT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-13). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.012%, afr); Associated with Inborn genetic diseases.

What condition is associated with CIT p.Asn786Ser (c.2357A>G)?

CIT p.Asn786Ser (c.2357A>G) is associated with Inborn genetic diseases, microcephaly 17, primary, autosomal recessive (ClinVar).

How common is CIT p.Asn786Ser (c.2357A>G) in the general population?

CIT p.Asn786Ser (c.2357A>G) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CIT p.Asn786Ser (c.2357A>G)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

CIT p.Asn786Ser

c.2357A>G · rs368057062 · VCV2441987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -5.65	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 0.95	GERP 1.9, phastCons 0.83
Regional constraint	o/e 0.64	unconstrained · MANE · 55 kb · p 2.1e-24 · regional, not allelic
Overall
CADD	17.45	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 N744S vs ClinVar N786S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,944 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00062% 10/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,327
European (non-Finnish)	8.47e-05%	1,180,026

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.Asn786Ser
Coding: c.2357A>G
MANE Select: NM_001206999
dbSNP: rs368057062
Type: single nucleotide variant
Location: chr12:119761003 (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

Also linked: microcephaly 17, primary, autosomal recessive

Similar variants

CIT p.Asn786Asp Uncertain significance ★ ⚠ same residue
CIT p.Arg1178Ter Pathogenic ★★ same condition
CIT p.Arg220Ter Pathogenic ★★ same condition
CIT c.4168+5G>A Uncertain significance ★★ same condition
CIT p.Ala1144Thr Uncertain significance ★★ ⚠ same condition
CIT p.Ala1527Val Uncertain significance ★★ ⚠ same condition
CIT p.Ala244Val Uncertain significance ★★ ⚠ same condition
CIT p.Ala495Ser 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-asn786ser (accessed [today's date]).

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