Is TCF20 p.Pro366Ala (c.1096C>G) pathogenic?

TCF20 p.Pro366Ala (c.1096C>G) is classified Uncertain significance in TCF20 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-21). AlphaMissense: likely pathogenic (0.9569); Absent from gnomAD v4.1.

How common is TCF20 p.Pro366Ala (c.1096C>G) in the general population?

TCF20 p.Pro366Ala (c.1096C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TCF20 p.Pro366Ala (c.1096C>G)?

AlphaMissense predicts likely pathogenic (score 0.9569) — an in-silico prediction, not a clinical call.

TCF20 p.Pro366Ala

c.1096C>G · rs1432716373 · VCV2128653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9569 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9569	likely pathogenic · top 8% in TCF20
REVEL	0.435	indeterminate
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	25.8	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.Pro366Ala
Coding: c.1096C>G
MANE Select: NM_001378418
dbSNP: rs1432716373
Type: single nucleotide variant
Location: chr22:42214210 (GRCh38)
Gene constraint: LOEUF 0.05 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.03
Residue 366: a UniProt-annotated variant site (in ddviba); the 'disordered' region

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

Similar variants

TCF20 p.Arg1907Ter Pathogenic ★★ same type
TCF20 p.Arg742Ter Pathogenic ★★ same type
TCF20 p.Gln1082Ter Pathogenic/Likely pathogenic ★★ same type
TCF20 p.Gln471Ter Pathogenic ★★ same type
TCF20 p.Gln754Ter Pathogenic ★★ same type
TCF20 p.Gln935Ter Pathogenic ★★ same type
TCF20 p.Trp1861Ter Pathogenic/Likely pathogenic ★★ same type
TCF20 p.Tyr264Ter 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/tcf20-p-pro366ala (accessed [today's date]).

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