Is CLTC p.Phe201Ser (c.602T>C) pathogenic?

CLTC p.Phe201Ser (c.602T>C) is classified Uncertain significance in CLTC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CLTC p.Phe201Ser (c.602T>C)?

CLTC p.Phe201Ser (c.602T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CLTC p.Phe201Ser (c.602T>C) in the general population?

CLTC p.Phe201Ser (c.602T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLTC p.Phe201Ser (c.602T>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

CLTC p.Phe201Ser

c.602T>C · rs2509362468 · VCV3146095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · 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	0.9992	likely pathogenic · top 3% in CLTC
REVEL	0.729	pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 23 kb · p 5.1e-71 · regional, not allelic
Overall
CADD	28.9	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: CLTC
Protein: p.Phe201Ser
Coding: c.602T>C
MANE Select: NM_004859
dbSNP: rs2509362468
Type: single nucleotide variant
Location: chr17:59648322 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.62 · 10 PDB
Residue 201: the 'wd40-like repeat 5' region; the 'globular terminal domain' region; a β-strand

Full CLTC 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

CLTC p.Ala1259Thr Uncertain significance ★★ same condition
CLTC p.Ala198Thr Uncertain significance ★★ ⚠ same condition
CLTC p.Arg923His Uncertain significance ★★ ⚠ same condition
CLTC p.Arg949His Uncertain significance ★★ ⚠ same condition
CLTC p.Asn1078Ser Uncertain significance ★★ ⚠ same condition
CLTC p.Asn1145Ser Uncertain significance ★★ ⚠ same condition
CLTC p.Asn340Ser Uncertain significance ★★ ⚠ same condition
CLTC p.Asn376Ser 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/cltc-p-phe201ser (accessed [today's date]).

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