Is TCF3 p.Ala296= (c.888C>G) pathogenic?

TCF3 p.Ala296= (c.888C>G) is classified Likely benign in TCF3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). Very rare (popmax 0.00783%, nfe).

How common is TCF3 p.Ala296= (c.888C>G) in the general population?

TCF3 p.Ala296= (c.888C>G) is very rare (popmax 0.00783%, nfe) (gnomAD).

TCF3 p.Ala296=

c.888C>G · rs34203855 · VCV1523239

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00783%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -2.8
Overall
CADD	0.674	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00783% European (non-Finnish) · 92/1,175,302 alleles

Filtering AF 0.0065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00603%

Overall 0.00625% 100/1,600,894 alleles · very rare exomes 86/1,448,724 · genomes 14/152,170 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00783%	12,775
Remaining individualsnot grpmax-eligible	0.00646%	15,489
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,226
Finnishnot grpmax-eligible	0.00325%	30,728
African / African-American	0.00134%	74,810

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.Ala296=
Coding: c.888C>G
MANE Select: NM_003200
dbSNP: rs34203855
Type: single nucleotide variant
Location: chr19:1621905 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.42 · 5 PDB
Residue 296: 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.Ala296Asp Uncertain significance ★★ ⚠ same residue
TCF3 p.Ala296Val Uncertain significance ★★ ⚠ same residue
TCF3 p.Arg321Ter Pathogenic ★★ same type
TCF3 p.Glu555Lys Pathogenic ★★ same type
TCF3 c.1327-3C>A Uncertain significance ★★ same type
TCF3 c.652+5A>G Uncertain significance ★★ same type
TCF3 c.955+3A>G Uncertain significance ★★ same type
TCF3 c.955+6G>A Uncertain significance ★★ 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-ala296 (accessed [today's date]).

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