Is TFRC p.Arg613Ser (c.1839G>T) pathogenic?

TFRC p.Arg613Ser (c.1839G>T) is classified Uncertain significance in TFRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-25). AlphaMissense: likely benign (0.2628); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TFRC p.Arg613Ser (c.1839G>T)?

TFRC p.Arg613Ser (c.1839G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TFRC p.Arg613Ser (c.1839G>T) in the general population?

TFRC p.Arg613Ser (c.1839G>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about TFRC p.Arg613Ser (c.1839G>T)?

AlphaMissense predicts likely benign (score 0.2628) — an in-silico prediction, not a clinical call.

TFRC p.Arg613Ser

c.1839G>T · rs925017138 · VCV1947922

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2628	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -4.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.8, phastCons 0.96
Regional constraint	o/e 0.90	unconstrained · MANE · 25 kb · p 0.0021 · regional, not allelic
Overall
CADD	14.89	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 0.000424% European (non-Finnish) · 5/1,180,052 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,052 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.Arg613Ser
Coding: c.1839G>T
MANE Select: NM_001128148
dbSNP: rs925017138
Type: single nucleotide variant
Location: chr3:196055140 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 24 PDB
Residue 613: an α-helix; the 'ligand-binding' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TFRC p.Ala166Val Uncertain significance ★★ ⚠ same condition
TFRC p.Ala196Thr Uncertain significance ★★ ⚠ same condition
TFRC p.Ala293Thr Uncertain significance ★★ ⚠ same condition
TFRC p.Ala540Val Uncertain significance ★★ ⚠ same condition
TFRC p.Ala72Ser Uncertain significance ★★ ⚠ same condition
TFRC p.Arg155His Uncertain significance ★★ ⚠ same condition
TFRC p.Arg719Cys Uncertain significance ★★ ⚠ same condition
TFRC p.Asn270Tyr Uncertain significance ★★ ⚠ same condition

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-arg613ser (accessed [today's date]).

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