Is CITED2 p.Ala25Pro (c.73G>C) pathogenic?

CITED2 p.Ala25Pro (c.73G>C) is classified Uncertain significance in CITED2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-24). AlphaMissense: ambiguous (0.5357); Very rare (popmax 0.00627%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CITED2 p.Ala25Pro (c.73G>C)?

CITED2 p.Ala25Pro (c.73G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CITED2 p.Ala25Pro (c.73G>C) in the general population?

CITED2 p.Ala25Pro (c.73G>C) is very rare (popmax 0.00627%, nfe) (gnomAD).

What do computational predictors say about CITED2 p.Ala25Pro (c.73G>C)?

AlphaMissense predicts ambiguous (score 0.5357) — an in-silico prediction, not a clinical call.

CITED2 p.Ala25Pro

c.73G>C · rs373786537 · VCV2631257

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5357 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5357	ambiguous
REVEL	0.408	indeterminate
SaProt	LLR -7.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 659 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	26.0	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 0.00627% European (non-Finnish) · 74/1,179,946 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00468% 75/1,602,582 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00627%	15,945
African / African-American	0.00134%	74,900

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.Ala25Pro
Coding: c.73G>C
MANE Select: NM_006079
dbSNP: rs373786537
Type: single nucleotide variant
Location: chr6:139373872 (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.Ala25Val Uncertain significance ★★ ⚠ same residue
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
CITED2 p.Ala91Gly 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-ala25pro (accessed [today's date]).

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