Is CLTC p.Glu1360Asp (c.4080A>C) pathogenic?

CLTC p.Glu1360Asp (c.4080A>C) is classified Uncertain significance in CLTC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-20). AlphaMissense: likely pathogenic (0.792); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 56.

What condition is associated with CLTC p.Glu1360Asp (c.4080A>C)?

CLTC p.Glu1360Asp (c.4080A>C) is associated with intellectual disability, autosomal dominant 56 (ClinVar).

How common is CLTC p.Glu1360Asp (c.4080A>C) in the general population?

CLTC p.Glu1360Asp (c.4080A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLTC p.Glu1360Asp (c.4080A>C)?

AlphaMissense predicts likely pathogenic (score 0.792) — an in-silico prediction, not a clinical call.

CLTC p.Glu1360Asp

c.4080A>C · rs2509154692 · VCV3237525

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.792 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, autosomal dominant 56

Computational evidence

Protein change
AlphaMissense	0.792	likely pathogenic
REVEL	0.354	indeterminate
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.9, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 1,389 bp · p 1.1e-33 · regional, not allelic
Overall
CADD	21.7	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: CLTC
Protein: p.Glu1360Asp
Coding: c.4080A>C
MANE Select: NM_004859
dbSNP: rs2509154692
Type: single nucleotide variant
Location: chr17:59683425 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.62 · 10 PDB
Residue 1360: the 'heavy chain arm' region; the 'proximal segment' region; the 'involved in binding clathrin light chain' region; a UniProt-annotated variant site (in mrd56)

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

Disease context

intellectual disability, autosomal dominant 56 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLTC p.Arg1165Ter Likely pathogenic ★★ same condition
CLTC p.Arg1251Ter Pathogenic/Likely pathogenic ★★ same condition
CLTC p.Arg1311Ter Likely pathogenic ★★ same condition
CLTC p.Arg63Ter Pathogenic ★★ same condition
CLTC p.Pro890Leu Pathogenic/Likely pathogenic ★★ same condition
CLTC p.Tyr1574Ter Pathogenic/Likely pathogenic ★★ same condition
CLTC c.4605+3T>A Uncertain significance ★★ same condition
CLTC p.Ala1496Gly 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-glu1360asp (accessed [today's date]).

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