Is TFRC p.Arg698= (c.2094A>C) pathogenic?

TFRC p.Arg698= (c.2094A>C) is classified Likely benign in TFRC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). Very rare (popmax 8.47e-05%, nfe).

How common is TFRC p.Arg698= (c.2094A>C) in the general population?

TFRC p.Arg698= (c.2094A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TFRC p.Arg698=

c.2094A>C · rs1716365892 · VCV1619804

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -3.7
Overall
CADD	0.317	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,996 alleles

Overall 6.84e-05% 1/1,461,856 alleles · very rare

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: TFRC
Protein: p.Arg698=
Coding: c.2094A>C
MANE Select: NM_001128148
dbSNP: rs1716365892
Type: single nucleotide variant
Location: chr3:196052131 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 24 PDB
Residue 698: the 'ligand-binding' region

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

Similar variants

TFRC p.Arg698Gln Uncertain significance ★ ⚠ same residue
TFRC c.1678-3C>T Uncertain significance ★★ same type
TFRC p.Ala166Val Uncertain significance ★★ ⚠ same type
TFRC p.Ala196Thr Uncertain significance ★★ ⚠ same type
TFRC p.Ala293Thr Uncertain significance ★★ ⚠ same type
TFRC p.Ala540Val Uncertain significance ★★ ⚠ same type
TFRC p.Ala72Ser Uncertain significance ★★ ⚠ same type
TFRC p.Arg155His 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/tfrc-p-arg698 (accessed [today's date]).

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