Is TF p.Arg162Cys (c.484C>T) pathogenic?

TF p.Arg162Cys (c.484C>T) is classified Uncertain significance in TF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: ambiguous (0.465); Very rare (popmax 0.01%, amr).

How common is TF p.Arg162Cys (c.484C>T) in the general population?

TF p.Arg162Cys (c.484C>T) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about TF p.Arg162Cys (c.484C>T)?

AlphaMissense predicts ambiguous (score 0.465) — an in-silico prediction, not a clinical call.

TF p.Arg162Cys

c.484C>T · VCV3455599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.465 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.465	ambiguous
REVEL	0.172	moderately benign-leaning
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 2.2
Regional constraint	o/e 0.85	unconstrained · MANE · 32 kb · p 8.3e-06 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.01% Admixed American · 6/60,002 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000805% 13/1,614,056 alleles · very rare exomes 12/1,461,884 · genomes 1/152,172 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
South Asian	0.0011%	91,090
European (non-Finnish)	0.000508%	196,674

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.Arg162Cys
Coding: c.484C>T
MANE Select: NM_001063
Type: single nucleotide variant
Location: chr3:133754653 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 162: the transferrin-like 1 domain

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

Similar variants

TF p.Arg162His 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-arg162cys (accessed [today's date]).

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