Is TGFB2 p.Phe32Ile (c.94T>A) pathogenic?

TGFB2 p.Phe32Ile (c.94T>A) is classified Uncertain significance in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-24). AlphaMissense: ambiguous (0.4022); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TGFB2 p.Phe32Ile (c.94T>A)?

TGFB2 p.Phe32Ile (c.94T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is TGFB2 p.Phe32Ile (c.94T>A) in the general population?

TGFB2 p.Phe32Ile (c.94T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TGFB2 p.Phe32Ile (c.94T>A)?

AlphaMissense predicts ambiguous (score 0.4022) — an in-silico prediction, not a clinical call.

TGFB2 p.Phe32Ile

c.94T>A · VCV4076483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4022 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4022	ambiguous
REVEL	0.114	moderately benign-leaning
SaProt	LLR -7.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 95 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	22.4	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.Phe32Ile
Coding: c.94T>A
MANE Select: NM_003238
Type: single nucleotide variant
Location: chr1:218346795 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 32: an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TGFB2 p.Phe32Leu Uncertain significance ★ ⚠ same residue
TGFB2 p.Phe32= Likely benign ★ same residue
TGFB2 p.Cys413= Benign/Likely benign ★★ same condition
TGFB2 p.Ala100Gly Uncertain significance ★ same condition
TGFB2 p.Ile239Asn Uncertain significance ★ ⚠ same condition
TGFB2 p.Tyr71His Uncertain significance ★ ⚠ same condition
TGFB2 c.1086+2T>C Likely pathogenic ★★ same type
TGFB2 c.346+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-phe32ile (accessed [today's date]).

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