Is CITED2 p.Val232Met (c.694G>A) pathogenic?

CITED2 p.Val232Met (c.694G>A) is classified Uncertain significance in CITED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-29). AlphaMissense: likely pathogenic (0.9981); Very rare (popmax 8.47e-05%, nfe).

How common is CITED2 p.Val232Met (c.694G>A) in the general population?

CITED2 p.Val232Met (c.694G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CITED2 p.Val232Met (c.694G>A)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

CITED2 p.Val232Met

c.694G>A · rs2482756744 · VCV2440091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic · top 5% in CITED2
REVEL	0.608	indeterminate
SaProt	LLR -10.00	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 102 bp · p 0.00024 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 6.84e-05% 1/1,461,862 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.Val232Met
Coding: c.694G>A
MANE Select: NM_006079
dbSNP: rs2482756744
Type: single nucleotide variant
Location: chr6:139373251 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI 0.90 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 52.07 · 4 PDB
Residue 232: an α-helix

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

Similar variants

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
CITED2 p.Gly194= Benign/Likely benign ★★ same type
CITED2 p.His160Leu Benign/Likely benign ★★ same type
CITED2 p.His46= Likely benign ★★ same type
CITED2 p.Pro209= Likely 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-val232met (accessed [today's date]).

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