Is CLTC p.Ala71fs (c.211_212del) pathogenic?

CLTC p.Ala71fs (c.211212del) is classified Likely pathogenic in CLTC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-27). Associated with intellectual disability, autosomal dominant 56.

What condition is associated with CLTC p.Ala71fs (c.211_212del)?

CLTC p.Ala71fs (c.211_212del) is associated with intellectual disability, autosomal dominant 56 (ClinVar).

CLTC p.Ala71fs

c.211_212del · VCV4081250

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 2 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: CLTC
Protein: p.Ala71fs
Coding: c.211_212del
MANE Select: NM_004859
Type: Microsatellite
Location: chr17:59644442 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.62 · 10 PDB
Residue 71: the 'wd40-like repeat 2' region; a β-strand; the 'globular terminal domain' region

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.Glu1564fs Pathogenic/Likely pathogenic ★★ same condition
CLTC p.Leu1217del Likely pathogenic ★★ same condition
CLTC p.Ser1524fs Pathogenic/Likely pathogenic ★★ same condition
CLTC p.Glu1475del Uncertain significance ★★ same condition
CLTC c.1647_1653del Pathogenic ★ same condition
CLTC p.Arg1481fs Likely pathogenic ★ same condition
CLTC p.Asp913fs Pathogenic ★ same condition
CLTC p.Ala71Thr Uncertain significance ★ ⚠ same residue

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-ala71fs (accessed [today's date]).

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