Is TCF20 p.Gly926Val (c.2777G>T) pathogenic?

TCF20 p.Gly926Val (c.2777G>T) is classified Uncertain significance in TCF20 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: ambiguous (0.3504); Very rare (popmax 8.48e-05%, nfe); Associated with developmental delay with variable intellectual impairment and behavioral abnormalities.

How common is TCF20 p.Gly926Val (c.2777G>T) in the general population?

TCF20 p.Gly926Val (c.2777G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about TCF20 p.Gly926Val (c.2777G>T)?

AlphaMissense predicts ambiguous (score 0.3504) — an in-silico prediction, not a clinical call.

TCF20 p.Gly926Val

Q: What condition is associated with TCF20 p.Gly926Val (c.2777G>T)?

TCF20 p.Gly926Val (c.2777G>T) is associated with developmental delay with variable intellectual impairment and behavioral abnormalities (ClinVar).

c.2777G>T · rs2147209717 · VCV1699287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

developmental delay with variable intellectual impairment and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.3504	ambiguous
REVEL	0.403	indeterminate
SaProt	LLR -5.63	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Overall
CADD	24.9	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,906 alleles

Overall 6.2e-05% 1/1,614,040 alleles · very rare exomes 1/1,461,738 · genomes 0/152,302 · joint denominator

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: TCF20
Protein: p.Gly926Val
Coding: c.2777G>T
MANE Select: NM_001378418
dbSNP: rs2147209717
Type: single nucleotide variant
Location: chr22:42212529 (GRCh38)
Gene constraint: LOEUF 0.05 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.03
Residue 926: a UniProt-annotated variant site (in ddviba); the 'disordered' region

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

Disease context

developmental delay with variable intellectual impairment and behavioral abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TCF20 p.Gly926Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
TCF20 p.Gly926= Likely benign ★ same residue
TCF20 p.Arg1907Ter Pathogenic ★★ same condition
TCF20 p.Arg742Ter Pathogenic ★★ same condition
TCF20 p.Gln1082Ter Pathogenic/Likely pathogenic ★★ same condition
TCF20 p.Gln471Ter Pathogenic ★★ same condition
TCF20 p.Gln754Ter Pathogenic ★★ same condition
TCF20 p.Trp1861Ter Pathogenic/Likely pathogenic ★★ 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-gly926val (accessed [today's date]).

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