Is TFRC p.Pro692Arg (c.2075C>G) pathogenic?

TFRC p.Pro692Arg (c.2075C>G) is classified Uncertain significance in TFRC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-03). AlphaMissense: ambiguous (0.504); Very rare (popmax 0.00134%, afr).

How common is TFRC p.Pro692Arg (c.2075C>G) in the general population?

TFRC p.Pro692Arg (c.2075C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about TFRC p.Pro692Arg (c.2075C>G)?

AlphaMissense predicts ambiguous (score 0.504) — an in-silico prediction, not a clinical call.

TFRC p.Pro692Arg

c.2075C>G · rs1027497110 · VCV1995343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.504	ambiguous
REVEL	0.472	indeterminate
SaProt	LLR -7.05	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 25 kb · p 0.0021 · regional, not allelic
Overall
CADD	24.3	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 0.00134% African / African-American · 1/74,894 alleles

Overall 6.2e-05% 1/1,613,958 alleles · very rare exomes 0/1,461,824 · genomes 1/152,134 · 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.Pro692Arg
Coding: c.2075C>G
MANE Select: NM_001128148
dbSNP: rs1027497110
Type: single nucleotide variant
Location: chr3:196052150 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 24 PDB
Residue 692: a turn; the 'ligand-binding' region

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

Similar variants

TFRC p.Pro692= Likely benign ★ 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-pro692arg (accessed [today's date]).

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