Is CITED2 p.Arg27Pro (c.80G>C) pathogenic?

CITED2 p.Arg27Pro (c.80G>C) is classified Uncertain significance in CITED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.9753); Very rare (popmax 0.000187%); Associated with Inborn genetic diseases.

What condition is associated with CITED2 p.Arg27Pro (c.80G>C)?

CITED2 p.Arg27Pro (c.80G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CITED2 p.Arg27Pro (c.80G>C) in the general population?

CITED2 p.Arg27Pro (c.80G>C) is very rare (popmax 0.000187%) (gnomAD).

What do computational predictors say about CITED2 p.Arg27Pro (c.80G>C)?

AlphaMissense predicts likely pathogenic (score 0.9753) — an in-silico prediction, not a clinical call.

CITED2 p.Arg27Pro

c.80G>C · rs1176150698 · VCV3145174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000187%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9753	likely pathogenic
REVEL	0.455	indeterminate
SaProt	LLR -5.73	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 659 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	28.1	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 0.000187%

Overall 0.000187% 3/1,603,210 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.Arg27Pro
Coding: c.80G>C
MANE Select: NM_006079
dbSNP: rs1176150698
Type: single nucleotide variant
Location: chr6:139373865 (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.Arg27Leu Uncertain significance ★ ⚠ same residue
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

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-arg27pro (accessed [today's date]).

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