Is CITED1 p.Leu45Pro (c.134T>C) pathogenic?

CITED1 p.Leu45Pro (c.134T>C) is classified Uncertain significance in CITED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: ambiguous (0.5324); Absent from gnomAD v4.1.

How common is CITED1 p.Leu45Pro (c.134T>C) in the general population?

CITED1 p.Leu45Pro (c.134T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CITED1 p.Leu45Pro (c.134T>C)?

AlphaMissense predicts ambiguous (score 0.5324) — an in-silico prediction, not a clinical call.

CITED1 p.Leu45Pro

c.134T>C · rs2519688821 · VCV2555108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5324 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5324	ambiguous
REVEL	0.739	pathogenic-leaning
SaProt	LLR -4.04	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 3.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 1,143 bp · p 0.00079 · regional, not allelic
Overall
CADD	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CITED1
Protein: p.Leu45Pro
Coding: c.134T>C
MANE Select: NM_001144887
dbSNP: rs2519688821
Type: single nucleotide variant
Location: chrX:72302171 (GRCh38)
Structure: AlphaFold pLDDT 60.42

Full CITED1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CITED1 p.Val162= Benign ★★ same type
CITED1 p.Ala118Thr Uncertain significance ★ ⚠ same type
CITED1 p.Ala130Glu Uncertain significance ★ ⚠ same type
CITED1 p.Ala187Val Uncertain significance ★ ⚠ same type
CITED1 p.Asn171Ser Uncertain significance ★ ⚠ same type
CITED1 p.Asn23His Uncertain significance ★ ⚠ same type
CITED1 p.Asn53Ser Uncertain significance ★ ⚠ same type
CITED1 p.Asn53Tyr Uncertain significance ★ ⚠ 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/cited1-p-leu45pro (accessed [today's date]).

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