Is TF p.Asp356Glu (c.1068T>A) pathogenic?

TF p.Asp356Glu (c.1068T>A) is classified Uncertain significance in TF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0875); Very rare (popmax 0.00593%, nfe).

How common is TF p.Asp356Glu (c.1068T>A) in the general population?

TF p.Asp356Glu (c.1068T>A) is very rare (popmax 0.00593%, nfe) (gnomAD).

What do computational predictors say about TF p.Asp356Glu (c.1068T>A)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

TF p.Asp356Glu

c.1068T>A · VCV4829110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -3.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1	GERP -3.5
Regional constraint	o/e 0.85	unconstrained · MANE · 32 kb · p 8.3e-06 · regional, not allelic
Overall
CADD	0.054	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

Grpmax group 0.00593% European (non-Finnish) · 70/1,179,964 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00434% 70/1,613,820 alleles · very rare exomes 68/1,461,782 · genomes 2/152,038 · 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: TF
Protein: p.Asp356Glu
Coding: c.1068T>A
MANE Select: NM_001063
Type: single nucleotide variant
Location: chr3:133759194 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 356: an α-helix

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

Similar variants

TF p.Asp356Asn Uncertain significance ★ ⚠ same residue
TF c.-18C>T Uncertain significance ★★ same type
TF p.Ala318Ser Uncertain significance ★★ ⚠ same type
TF p.Ala72Val Uncertain significance ★★ ⚠ same type
TF p.Gln264Glu Uncertain significance ★★ ⚠ same type
TF p.Gln559Leu Uncertain significance ★★ ⚠ same type
TF p.Ile229Thr Uncertain significance ★★ ⚠ same type
TF p.Thr112Ala 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/tf-p-asp356glu (accessed [today's date]).

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