Is TGFB2 p.Arg362Ser (c.1086G>T) pathogenic?

TGFB2 p.Arg362Ser (c.1086G>T) is classified Uncertain significance in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-30). AlphaMissense: ambiguous (0.5558); Very rare (popmax 0.00017%, nfe).

How common is TGFB2 p.Arg362Ser (c.1086G>T) in the general population?

TGFB2 p.Arg362Ser (c.1086G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about TGFB2 p.Arg362Ser (c.1086G>T)?

AlphaMissense predicts ambiguous (score 0.5558) — an in-silico prediction, not a clinical call.

TGFB2 p.Arg362Ser

c.1086G>T · VCV3360759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5558 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5558	ambiguous
REVEL	0.296	indeterminate
SaProt	LLR -5.36	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 95 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	22.3	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 0.00017% European (non-Finnish) · 2/1,177,522 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,608,056 alleles · very rare exomes 2/1,455,924 · genomes 0/152,132 · 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: TGFB2
Protein: p.Arg362Ser
Coding: c.1086G>T
MANE Select: NM_003238
Type: single nucleotide variant
Location: chr1:218437496 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 362: a UniProt-annotated variant site (in lds4); an α-helix

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

Similar variants

TGFB2 p.Arg362= Uncertain significance ★ 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
TGFB2 p.Arg131Ter 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-arg362ser (accessed [today's date]).

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