Is CLTC p.Met1302fs (c.3905_3911del) pathogenic?

CLTC p.Met1302fs (c.39053911del) is classified Likely pathogenic in CLTC (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with intellectual disability, autosomal dominant 56.

What condition is associated with CLTC p.Met1302fs (c.3905_3911del)?

CLTC p.Met1302fs (c.3905_3911del) is associated with intellectual disability, autosomal dominant 56 (ClinVar).

How common is CLTC p.Met1302fs (c.3905_3911del) in the general population?

CLTC p.Met1302fs (c.3905_3911del) is absent from gnomAD (gnomAD).

CLTC p.Met1302fs

c.3905_3911del · rs2509154133 · VCV2663814

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability, autosomal dominant 56

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 25 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.049	GERP -1.9, phastCons 0.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLTC
Protein: p.Met1302fs
Coding: c.3905_3911del
MANE Select: NM_004859
dbSNP: rs2509154133
Type: Deletion
Location: chr17:59683125 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.62 · 10 PDB
Residue 1302: 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.Tyr1598fs Pathogenic ★★ same condition
CLTC p.Asn678fs Likely pathogenic ★ same condition
CLTC p.Asp1366fs Likely pathogenic ★ same condition
CLTC p.Ile699fs Likely pathogenic ★ same condition
CLTC p.Ile882_Tyr883insTer Pathogenic ★ same condition
CLTC p.Leu585fs Likely pathogenic ★ same condition
CLTC p.Met1159_Ala1160insTer Pathogenic ★ same condition
CLTC p.Phe1471del Likely pathogenic ★ 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-met1302fs (accessed [today's date]).

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