Is TF p.Val675Ile (c.2023G>A) pathogenic?

TF p.Val675Ile (c.2023G>A) is classified Uncertain significance in TF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.0904); Very rare (popmax 0.004%, afr).

How common is TF p.Val675Ile (c.2023G>A) in the general population?

TF p.Val675Ile (c.2023G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about TF p.Val675Ile (c.2023G>A)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

TF p.Val675Ile

c.2023G>A · VCV3325584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.90	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 -0.22	GERP -4.3
Regional constraint	o/e 0.85	unconstrained · MANE · 32 kb · p 8.3e-06 · regional, not allelic
Overall
CADD	0.971	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 0.004% African / African-American · 3/74,926 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000991% 16/1,613,734 alleles · very rare exomes 14/1,461,536 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,975
European (non-Finnish)	0.0011%	90,771

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.Val675Ile
Coding: c.2023G>A
MANE Select: NM_001063
Type: single nucleotide variant
Location: chr3:133777199 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 675: an α-helix; the transferrin-like 2 domain

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

Similar variants

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
TF p.Val270Asp 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-val675ile (accessed [today's date]).

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