Is CITED2 p.Pro24Ser (c.70C>T) pathogenic?

CITED2 p.Pro24Ser (c.70C>T) is classified Uncertain significance in CITED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). AlphaMissense: ambiguous (0.3698); Ultra-rare (popmax 0.0183%, amr); Associated with Inborn genetic diseases.

What condition is associated with CITED2 p.Pro24Ser (c.70C>T)?

CITED2 p.Pro24Ser (c.70C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CITED2 p.Pro24Ser (c.70C>T) in the general population?

CITED2 p.Pro24Ser (c.70C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about CITED2 p.Pro24Ser (c.70C>T)?

AlphaMissense predicts ambiguous (score 0.3698) — an in-silico prediction, not a clinical call.

CITED2 p.Pro24Ser

c.70C>T · rs745469955 · VCV3145173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3698 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3698	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -7.60	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 659 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	23.4	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 0.0183% Admixed American · 11/60,004 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00169% 27/1,602,328 alleles · ultra-rare exomes 19/1,450,148 · genomes 8/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,455
Middle Eastern	0.017%	5,894
Remaining individualsnot grpmax-eligible	0.00641%	15,597
European (non-Finnish)	0.000932%	107,268

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.Pro24Ser
Coding: c.70C>T
MANE Select: NM_006079
dbSNP: rs745469955
Type: single nucleotide variant
Location: chr6:139373875 (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.Ala25Pro Uncertain significance ★★ same condition
CITED2 p.Ala25Val Uncertain significance ★★ same condition
CITED2 p.Pro128Ser 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-pro24ser (accessed [today's date]).

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