Is TCF4 p.Pro485fs (c.1454_1455del) pathogenic?

TCF4 p.Pro485fs (c.14541455del) is classified Likely pathogenic in TCF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-19). No gnomAD frequency available for this variant; Associated with Pitt-Hopkins syndrome.

What condition is associated with TCF4 p.Pro485fs (c.1454_1455del)?

TCF4 p.Pro485fs (c.1454_1455del) is associated with Pitt-Hopkins syndrome (ClinVar).

How common is TCF4 p.Pro485fs (c.1454_1455del) in the general population?

TCF4 p.Pro485fs (c.1454_1455del) is no gnomAD frequency available for this variant (gnomAD).

TCF4 p.Pro485fs

c.1454_1455del · rs2144676461 · VCV1325854

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Pitt-Hopkins syndrome

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 16 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1

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: TCF4
Protein: p.Pro485fs
Coding: c.1454_1455del
MANE Select: NM_001083962
dbSNP: rs2144676461
Type: Deletion
Location: chr18:55234579 (GRCh38)
Gene constraint: LOEUF 0.096 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.08 · 5 PDB
Residue 485: a UniProt-annotated variant site (in pths); the 'disordered' region

Full TCF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Pitt-Hopkins syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TCF4 p.Gln670fs Pathogenic ★★★ same condition
TCF4 c.991-8_991-4del Likely benign ★★★ same condition
TCF4 p.Arg157fs Pathogenic ★★ same condition
TCF4 p.Arg389_Leu390insTer Pathogenic/Likely pathogenic ★★ same condition
TCF4 p.Arg576fs Pathogenic/Likely pathogenic ★★ same condition
TCF4 p.Leu139fs Pathogenic/Likely pathogenic ★★ same condition
TCF4 p.Leu379fs Pathogenic ★★ same condition
TCF4 p.Ser510fs 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/tcf4-p-pro485fs (accessed [today's date]).

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