Is CITED2 p.Pro128Ser (c.382C>T) pathogenic?

CITED2 p.Pro128Ser (c.382C>T) is classified Uncertain significance in CITED2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-31). AlphaMissense: ambiguous (0.3909); Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with CITED2 p.Pro128Ser (c.382C>T)?

CITED2 p.Pro128Ser (c.382C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CITED2 p.Pro128Ser (c.382C>T) in the general population?

CITED2 p.Pro128Ser (c.382C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CITED2 p.Pro128Ser (c.382C>T)?

AlphaMissense predicts ambiguous (score 0.3909) — an in-silico prediction, not a clinical call.

CITED2 p.Pro128Ser

c.382C>T · rs767546559 · VCV930141

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3909	ambiguous
REVEL	0.452	indeterminate
SaProt	LLR -6.78	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 659 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	25.2	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 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00123% 18/1,461,838 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
South Asian	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,494
African / African-American	0.00133%	75,056
European (non-Finnish)	0.000932%	107,273

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.Pro128Ser
Coding: c.382C>T
MANE Select: NM_006079
dbSNP: rs767546559
Type: single nucleotide variant
Location: chr6:139373563 (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

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

Similar variants

CITED2 p.Pro128Leu Uncertain significance ★ ⚠ same residue
CITED2 p.Ala25Pro Uncertain significance ★★ ⚠ same condition
CITED2 p.Ala25Val Uncertain significance ★★ ⚠ same condition
CITED2 p.Ala203Val Uncertain significance ★ ⚠ same condition
CITED2 p.Ala206Val Uncertain significance ★ ⚠ same condition
CITED2 p.Ala211Thr Uncertain significance ★ ⚠ same condition
CITED2 p.Ala65Ser Uncertain significance ★ ⚠ same condition
CITED2 p.Ala7Val 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/cited2-p-pro128ser (accessed [today's date]).

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