Is TSFM p.Val12Phe (c.34G>T) pathogenic?

TSFM p.Val12Phe (c.34G>T) is classified Uncertain significance in TSFM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0889); No allele count reported in gnomAD v4.1 (AN 1,596,416).

How common is TSFM p.Val12Phe (c.34G>T) in the general population?

TSFM p.Val12Phe (c.34G>T) is no allele count reported in gnomAD v4.1 (AN 1,596,416) (gnomAD).

What do computational predictors say about TSFM p.Val12Phe (c.34G>T)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

TSFM p.Val12Phe

c.34G>T · rs2540941601 · VCV1920353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,416)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -7.67	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 0.58	GERP -0.83
Regional constraint	o/e 1.15	unconstrained · MANE · 4,331 bp · p 0.04 · regional, not allelic
Overall
CADD	11.97	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

No allele count reported in gnomAD v4.1 (AN 1,596,416). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TSFM
Protein: p.Val12Phe
Coding: c.34G>T
MANE Select: NM_005726
dbSNP: rs2540941601
Type: single nucleotide variant
Location: chr12:57782835 (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.Val12= Likely benign ★ 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-val12phe (accessed [today's date]).

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