Is TGM1 p.Pro173= (c.519C>T) pathogenic?

TGM1 p.Pro173= (c.519C>T) is classified Conflicting classifications of pathogenicity in TGM1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0606%, nfe); Associated with autosomal recessive congenital ichthyosis 1.

What condition is associated with TGM1 p.Pro173= (c.519C>T)?

TGM1 p.Pro173= (c.519C>T) is associated with autosomal recessive congenital ichthyosis 1 (ClinVar).

How common is TGM1 p.Pro173= (c.519C>T) in the general population?

TGM1 p.Pro173= (c.519C>T) is ultra-rare (popmax 0.0606%, nfe) (gnomAD).

TGM1 p.Pro173=

c.519C>T · rs139811103 · VCV766335

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0606%, nfe)

Conditions

autosomal recessive congenital ichthyosis 1

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 -11	GERP -5.1
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0606% European (non-Finnish) · 715/1,180,036 alleles

Filtering AF 0.0568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0554%

Overall 0.048% 774/1,613,956 alleles · ultra-rare exomes 731/1,461,800 · genomes 43/152,156 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0606%	1,650
Remaining individualsnot grpmax-eligible	0.0336%	2,975
Admixed American	0.0283%	3,529
African / African-American	0.0147%	6,810
Finnishnot grpmax-eligible	0.0141%	7,106
South Asian	0.0011%	91,086

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: TGM1
Protein: p.Pro173=
Coding: c.519C>T
MANE Select: NM_000359
dbSNP: rs139811103
Type: single nucleotide variant
Location: chr14:24260688 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

Full TGM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive congenital ichthyosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TGM1 c.1159+1G>T Pathogenic ★★ same condition
TGM1 c.1645+1G>T Pathogenic/Likely pathogenic ★★ same condition
TGM1 c.2226-2A>G Pathogenic/Likely pathogenic ★★ same condition
TGM1 c.319+2T>C Likely pathogenic ★★ same condition
TGM1 c.876+2T>C Pathogenic/Likely pathogenic ★★ same condition
TGM1 c.877-2A>G Pathogenic ★★ same condition
TGM1 c.984+1G>A Pathogenic/Likely pathogenic ★★ same condition
TGM1 p.Arg106Ter Pathogenic ★★ 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/tgm1-p-pro173 (accessed [today's date]).

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