Is CTH p.Cys252Phe (c.755G>T) pathogenic?

CTH p.Cys252Phe (c.755G>T) is classified Uncertain significance in CTH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.9637); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTH p.Cys252Phe (c.755G>T)?

CTH p.Cys252Phe (c.755G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTH p.Cys252Phe (c.755G>T) in the general population?

CTH p.Cys252Phe (c.755G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTH p.Cys252Phe (c.755G>T)?

AlphaMissense predicts likely pathogenic (score 0.9637) — an in-silico prediction, not a clinical call.

CTH p.Cys252Phe

c.755G>T · VCV3837130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9637 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9637	likely pathogenic · top 3% in CTH
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -14.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	26.8	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

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: CTH
Protein: p.Cys252Phe
Coding: c.755G>T
MANE Select: NM_014312 · reported on NM_001902
Type: single nucleotide variant
Location: chr1:70432113 (GRCh38)
Structure: AlphaFold pLDDT 80.30

Full CTH 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

CTH p.Asp181Asn Uncertain significance ★★ ⚠ same condition
CTH p.Thr158Ile Uncertain significance ★★ ⚠ same condition
CTH p.Ala103Ser Uncertain significance ★ ⚠ same condition
CTH p.Ala146Pro Uncertain significance ★ ⚠ same condition
CTH p.Ala245Thr Uncertain significance ★ ⚠ same condition
CTH p.Ala51Thr Uncertain significance ★ ⚠ same condition
CTH p.Ala6Thr Uncertain significance ★ ⚠ same condition
CTH p.Arg62Pro 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/cth-p-cys252phe (accessed [today's date]).

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