Is TCF20 p.Arg899Pro (c.2696G>C) pathogenic?

TCF20 p.Arg899Pro (c.2696G>C) is classified Uncertain significance in TCF20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.5793); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TCF20 p.Arg899Pro (c.2696G>C)?

TCF20 p.Arg899Pro (c.2696G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TCF20 p.Arg899Pro (c.2696G>C) in the general population?

TCF20 p.Arg899Pro (c.2696G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TCF20 p.Arg899Pro (c.2696G>C)?

AlphaMissense predicts likely pathogenic (score 0.5793) — an in-silico prediction, not a clinical call.

TCF20 p.Arg899Pro

c.2696G>C · VCV4632859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5793	likely pathogenic
REVEL	0.202	benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TCF20
Protein: p.Arg899Pro
Coding: c.2696G>C
MANE Select: NM_001378418
Type: single nucleotide variant
Location: chr22:42212610 (GRCh38)
Gene constraint: LOEUF 0.05 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.03
Residue 899: a UniProt-annotated variant site (in ddviba)

Full TCF20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TCF20 p.Arg899Cys Uncertain significance ★ ⚠ same residue
TCF20 p.Arg742Ter Pathogenic ★★ same condition
TCF20 p.Ala1160Thr Uncertain significance ★★ ⚠ same condition
TCF20 p.Ala1226Gly Uncertain significance ★★ ⚠ same condition
TCF20 p.Ala1507Thr Uncertain significance ★★ ⚠ same condition
TCF20 p.Ala373Val Uncertain significance ★★ ⚠ same condition
TCF20 p.Ala586Thr Uncertain significance ★★ ⚠ same condition
TCF20 p.Ala688Thr Uncertain significance ★★ ⚠ 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/tcf20-p-arg899pro (accessed [today's date]).

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