Is TCF3 p.Pro201Arg (c.602C>G) pathogenic?

TCF3 p.Pro201Arg (c.602C>G) is classified Uncertain significance in TCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). AlphaMissense: likely benign (0.1397); Very rare (popmax 0.00205%, amr).

How common is TCF3 p.Pro201Arg (c.602C>G) in the general population?

TCF3 p.Pro201Arg (c.602C>G) is very rare (popmax 0.00205%, amr) (gnomAD).

What do computational predictors say about TCF3 p.Pro201Arg (c.602C>G)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

TCF3 p.Pro201Arg

c.602C>G · rs770464889 · VCV2914745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00205%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 39 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00205% Admixed American · 1/48,746 alleles

Overall 0.000131% 2/1,529,808 alleles · very rare exomes 1/1,377,728 · genomes 1/152,080 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00205%	48,746
Remaining individualsnot grpmax-eligible	0.0017%	58,854

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.Pro201Arg
Coding: c.602C>G
MANE Select: NM_003200
dbSNP: rs770464889
Type: single nucleotide variant
Location: chr19:1622363 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.42 · 5 PDB
Residue 201: the 'disordered' region

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

Similar variants

TCF3 p.Pro201Leu Uncertain significance ★★ ⚠ same residue
TCF3 p.Pro201= Likely benign ★★ 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-pro201arg (accessed [today's date]).

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