Is TGFB1 p.Ser287Cys (c.859A>T) pathogenic?

TGFB1 p.Ser287Cys (c.859A>T) is classified Uncertain significance in TGFB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-23). AlphaMissense: likely pathogenic (0.5768); Absent from gnomAD v4.1.

How common is TGFB1 p.Ser287Cys (c.859A>T) in the general population?

TGFB1 p.Ser287Cys (c.859A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TGFB1 p.Ser287Cys (c.859A>T)?

AlphaMissense predicts likely pathogenic (score 0.5768) — an in-silico prediction, not a clinical call.

TGFB1 p.Ser287Cys

c.859A>T · rs2513381057 · VCV2110344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5768 · 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	0.5768	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -9.91	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 7.8	GERP 1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	32.0	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: TGFB1
Protein: p.Ser287Cys
Coding: c.859A>T
MANE Select: NM_000660
dbSNP: rs2513381057
Type: single nucleotide variant
Location: chr19:41341884 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.11 · 22 PDB
Residue 287: an α-helix

Full TGFB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TGFB1 p.Arg218Cys Pathogenic ★★ same type
TGFB1 p.Arg218His Pathogenic/Likely pathogenic ★★ ⚠ same type
TGFB1 p.Tyr171Cys Likely pathogenic ★★ same type
TGFB1 c.1014+5G>A Uncertain significance ★★ same type
TGFB1 p.Arg152Trp Uncertain significance ★★ ⚠ same type
TGFB1 p.Arg185Trp Uncertain significance ★★ ⚠ same type
TGFB1 p.Arg277Cys Uncertain significance ★★ ⚠ same type
TGFB1 p.Arg385Gly Uncertain significance ★★ 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/tgfb1-p-ser287cys (accessed [today's date]).

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