Is CITED2 p.Pro84Ser (c.250C>T) pathogenic?

CITED2 p.Pro84Ser (c.250C>T) is classified Uncertain significance in CITED2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-22). AlphaMissense: likely benign (0.0423); Very rare (popmax 0.0022%, sas); Associated with CITED2-related disorder.

What condition is associated with CITED2 p.Pro84Ser (c.250C>T)?

CITED2 p.Pro84Ser (c.250C>T) is associated with CITED2-related disorder (ClinVar).

How common is CITED2 p.Pro84Ser (c.250C>T) in the general population?

CITED2 p.Pro84Ser (c.250C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CITED2 p.Pro84Ser (c.250C>T)?

AlphaMissense predicts likely benign (score 0.0423) — an in-silico prediction, not a clinical call.

CITED2 p.Pro84Ser

c.250C>T · VCV3347207

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0423 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CITED2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0423	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.67	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 2.3	GERP -1.3, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 659 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	15.55	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 0.0022% South Asian · 2/91,070 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,458,822 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: CITED2
Protein: p.Pro84Ser
Coding: c.250C>T
MANE Select: NM_006079
Type: single nucleotide variant
Location: chr6:139373695 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI 0.90 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 52.07 · 4 PDB

Full CITED2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CITED2-related disorder

Similar variants

CITED2 c.-8-179G>C Uncertain significance ★ same condition
CITED2 p.Thr149Ile Uncertain significance ★ ⚠ same condition
CITED2 c.-8-187T>C Likely benign same condition
CITED2 p.Gly185_Gly186insSerSerThrProGlyGlySerGlySerSerSerGlyGly Uncertain significance ★ same condition
CITED2 p.Ala25Pro Uncertain significance ★★ ⚠ same type
CITED2 p.Ala25Val Uncertain significance ★★ ⚠ same type
CITED2 p.Pro128Ser Uncertain significance ★★ ⚠ same type
CITED2 p.Ala7= Benign ★★ 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/cited2-p-pro84ser (accessed [today's date]).

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