Is TFRC p.Ala487= (c.1461G>T) pathogenic?

TFRC p.Ala487= (c.1461G>T) is classified Likely benign in TFRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-27). Very rare (popmax 0.000934%, nfe).

How common is TFRC p.Ala487= (c.1461G>T) in the general population?

TFRC p.Ala487= (c.1461G>T) is very rare (popmax 0.000934%, nfe) (gnomAD).

TFRC p.Ala487=

c.1461G>T · VCV4701366

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000934%, 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 0.69	GERP -0.64, phastCons 0.62
Overall
CADD	3.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000934% European (non-Finnish) · 11/1,178,014 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000685% 11/1,607,002 alleles · very rare exomes 11/1,454,710 · genomes 0/152,292 · 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: TFRC
Protein: p.Ala487=
Coding: c.1461G>T
MANE Select: NM_001128148
Type: single nucleotide variant
Location: chr3:196062589 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 24 PDB

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

Similar variants

TFRC p.Ala487Ser Uncertain significance ★ ⚠ same residue
TFRC p.Ala487Thr Uncertain significance ★ ⚠ same residue
TFRC p.Ala487Val 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

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-ala487 (accessed [today's date]).

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