Is TGFB2 p.Asp384Val (c.1151A>T) pathogenic?

TGFB2 p.Asp384Val (c.1151A>T) is classified Uncertain significance in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely pathogenic (0.6355); Absent from gnomAD v4.1.

How common is TGFB2 p.Asp384Val (c.1151A>T) in the general population?

TGFB2 p.Asp384Val (c.1151A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TGFB2 p.Asp384Val (c.1151A>T)?

AlphaMissense predicts likely pathogenic (score 0.6355) — an in-silico prediction, not a clinical call.

TGFB2 p.Asp384Val

c.1151A>T · VCV3371874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6355 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6355	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 95 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	23.6	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: TGFB2
Protein: p.Asp384Val
Coding: c.1151A>T
MANE Select: NM_003238
Type: single nucleotide variant
Location: chr1:218441268 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 384: a UniProt-annotated variant site (in lds4); a β-strand

Full TGFB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TGFB2 p.Asp384His Uncertain significance ★ ⚠ same residue
TGFB2 p.Asp384= Likely benign ★ same residue
TGFB2 c.1086+2T>C Likely pathogenic ★★ same type
TGFB2 c.346+1G>A Pathogenic/Likely pathogenic ★★ same type
TGFB2 c.346+1G>T Likely pathogenic ★★ same type
TGFB2 c.510+1G>A Likely pathogenic ★★ same type
TGFB2 c.932+1G>A Pathogenic/Likely pathogenic ★★ same type
TGFB2 c.933-1G>A Pathogenic/Likely 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/tgfb2-p-asp384val (accessed [today's date]).

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