Is TCF3 p.Phe293del (c.878_880del) pathogenic?

TCF3 p.Phe293del (c.878880del) is classified Uncertain significance in TCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-17). Very rare (popmax 0.00268%, afr).

How common is TCF3 p.Phe293del (c.878_880del) in the general population?

TCF3 p.Phe293del (c.878_880del) is very rare (popmax 0.00268%, afr) (gnomAD).

TCF3 p.Phe293del

c.878_880del · rs748560717 · VCV2067078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 1.1, phastCons 1
Overall
CADD	15.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,754 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.00106% 17/1,601,682 alleles · very rare exomes 16/1,450,092 · genomes 1/151,590 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00323%	30,995
African / African-Americangrpmax	0.00268%	37,377
East Asian	0.00225%	44,446
Admixed American	0.00172%	58,306
European (non-Finnish)	0.000936%	106,840

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TCF3
Protein: p.Phe293del
Coding: c.878_880del
MANE Select: NM_003200
dbSNP: rs748560717
Type: Deletion
Location: chr19:1621913 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.42 · 5 PDB
Residue 293: a UniProt-annotated variant site (in agm8b; decreased protein abundance); the 'disordered' region

Full TCF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TCF3 p.Phe293Leu Uncertain significance ★★ ⚠ same residue
TCF3 p.Phe293Ser Conflicting classifications of pathogenicity ★ same residue
TCF3 p.Phe293= Likely benign ★ same residue
TCF3 c.1093+15_1093+48del Likely benign ★★ same type
TCF3 c.1167+15del Benign/Likely benign ★★ same type
TCF3 p.Ile393fs Pathogenic ★ same type
TCF3 p.Ser202fs Pathogenic ★ same type
TCF3 p.Ser224fs Pathogenic ★ same type

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/tcf3-p-phe293del (accessed [today's date]).

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