Is TSFM p.Pro30Ser (c.88C>T) pathogenic?

TSFM p.Pro30Ser (c.88C>T) is classified Uncertain significance in TSFM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-09). AlphaMissense: likely benign (0.0813); Absent from gnomAD v4.1.

How common is TSFM p.Pro30Ser (c.88C>T) in the general population?

TSFM p.Pro30Ser (c.88C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TSFM p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

TSFM p.Pro30Ser

c.88C>T · rs2540942790 · VCV1895979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.43, phastCons 0.71
Regional constraint	o/e 1.15	unconstrained · MANE · 4,331 bp · p 0.04 · regional, not allelic
Overall
CADD	15.78	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: TSFM
Protein: p.Pro30Ser
Coding: c.88C>T
MANE Select: NM_005726
dbSNP: rs2540942790
Type: single nucleotide variant
Location: chr12:57783140 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.87 · 1 PDB

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

Similar variants

TSFM p.Pro30Leu Uncertain significance ★ ⚠ same residue
TSFM c.231+1G>A Likely pathogenic ★★ same type
TSFM c.232-2A>G Likely pathogenic ★★ same type
TSFM c.484-1G>A Likely pathogenic ★★ same type
TSFM c.484-1G>T Likely pathogenic ★★ same type
TSFM c.57+1G>A Likely pathogenic ★★ same type
TSFM c.571+1G>C Pathogenic/Likely pathogenic ★★ same type
TSFM p.Arg201Ter 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/tsfm-p-pro30ser (accessed [today's date]).

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