Is TG p.Pro880Arg (c.2639C>G) pathogenic?

TG p.Pro880Arg (c.2639C>G) is classified Uncertain significance in TG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). AlphaMissense: likely benign (0.3045); Ultra-rare (popmax 0.0517%, amr); Associated with Inborn genetic diseases.

What condition is associated with TG p.Pro880Arg (c.2639C>G)?

TG p.Pro880Arg (c.2639C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TG p.Pro880Arg (c.2639C>G) in the general population?

TG p.Pro880Arg (c.2639C>G) is ultra-rare (popmax 0.0517%, amr) (gnomAD).

What do computational predictors say about TG p.Pro880Arg (c.2639C>G)?

AlphaMissense predicts likely benign (score 0.3045) — an in-silico prediction, not a clinical call.

TG p.Pro880Arg

c.2639C>G · rs201893722 · VCV2499262

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3045 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0517%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3045	likely benign
REVEL	0.574	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 268 kb · p 0.022 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0517% Admixed American · 31/59,946 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00279% 45/1,612,234 alleles · ultra-rare exomes 18/1,460,032 · genomes 27/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0517%	1,934
Remaining individualsnot grpmax-eligible	0.0192%	5,203
African / African-American	0.00267%	37,485

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: TG
Protein: p.Pro880Arg
Coding: c.2639C>G
MANE Select: NM_003235
dbSNP: rs201893722
Type: single nucleotide variant
Location: chr8:132888446 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 880: the thyroglobulin type-1 7 domain

Full TG 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

TG p.Pro880Leu Uncertain significance ★★ same residue
TG p.Pro880= Likely benign ★ same residue
TG p.Ala1033Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1419Glu Uncertain significance ★★ same condition
TG p.Ala1419Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1583Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1631Ser Uncertain significance ★★ ⚠ same condition
TG p.Ala402Gly 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/tg-p-pro880arg (accessed [today's date]).

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