Is CITED4 p.Pro50Leu (c.149C>T) pathogenic?

CITED4 p.Pro50Leu (c.149C>T) is classified Uncertain significance in CITED4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.0928); Very rare (popmax 0.00261%, sas).

How common is CITED4 p.Pro50Leu (c.149C>T) in the general population?

CITED4 p.Pro50Leu (c.149C>T) is very rare (popmax 0.00261%, sas) (gnomAD).

What do computational predictors say about CITED4 p.Pro50Leu (c.149C>T)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

CITED4 p.Pro50Leu

c.149C>T · rs1558053456 · VCV3145175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00261%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.66, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 551 bp · p 0.00038 · regional, not allelic
Overall
CADD	14.59	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00261% South Asian · 1/38,272 alleles

Filtering AF 3.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3e-05%

Overall 0.000272% 3/1,101,206 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00261%	38,272
European (non-Finnish)	0.0002%	499,214

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: CITED4
Protein: p.Pro50Leu
Coding: c.149C>T
MANE Select: NM_133467
dbSNP: rs1558053456
Type: single nucleotide variant
Location: chr1:40861979 (GRCh38)
Gene constraint: LOEUF 1.958 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.74
Residue 50: the 'disordered' region

Full CITED4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CITED4 p.Ala116Thr Uncertain significance ★ ⚠ same type
CITED4 p.Ala22Gly Uncertain significance ★ ⚠ same type
CITED4 p.Ala28Val Uncertain significance ★ ⚠ same type
CITED4 p.Ala93Glu Uncertain significance ★ ⚠ same type
CITED4 p.Arg155Cys Uncertain significance ★ ⚠ same type
CITED4 p.Arg155Gly Uncertain significance ★ ⚠ same type
CITED4 p.Arg30Gln Uncertain significance ★ ⚠ same type
CITED4 p.Arg30Trp 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/cited4-p-pro50leu (accessed [today's date]).

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