Is CDT1 p.Ala347Val (c.1040C>T) pathogenic?

CDT1 p.Ala347Val (c.1040C>T) is classified Conflicting classifications of pathogenicity in CDT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-08-01). AlphaMissense: likely benign (0.0672); Ultra-rare (popmax 0.0336%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDT1 p.Ala347Val (c.1040C>T)?

CDT1 p.Ala347Val (c.1040C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDT1 p.Ala347Val (c.1040C>T) in the general population?

CDT1 p.Ala347Val (c.1040C>T) is ultra-rare (popmax 0.0336%, eas) (gnomAD).

What do computational predictors say about CDT1 p.Ala347Val (c.1040C>T)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

CDT1 p.Ala347Val

c.1040C>T · VCV3489783

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0336%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.96	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 2.8	GERP -1.5, phastCons 0.94
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	14.8	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

Grpmax group 0.0336% East Asian · 15/44,692 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00249% 40/1,608,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0336%	2,979
Admixed American	0.00336%	29,794
Remaining individualsnot grpmax-eligible	0.00322%	31,067
African / African-American	0.00267%	37,419
European (non-Finnish)	0.00161%	62,004

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: CDT1
Protein: p.Ala347Val
Coding: c.1040C>T
MANE Select: NM_030928
Type: single nucleotide variant
Location: chr16:88806592 (GRCh38)
Gene constraint: LOEUF 1.737 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.51 · 6 PDB
Residue 347: an α-helix

Full CDT1 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

CDT1 p.Ala11Val Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala144Ser Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala167Thr Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala217Val Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala414Ser Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala431Thr Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala534Val Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala90Thr 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/cdt1-p-ala347val (accessed [today's date]).

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