Is TGM1 p.Pro20= (c.60T>C) pathogenic?

TGM1 p.Pro20= (c.60T>C) is classified Likely benign in TGM1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-19). Ultra-rare (popmax 0.0506%, afr); Associated with autosomal recessive congenital ichthyosis 1.

What condition is associated with TGM1 p.Pro20= (c.60T>C)?

TGM1 p.Pro20= (c.60T>C) is associated with autosomal recessive congenital ichthyosis 1 (ClinVar).

How common is TGM1 p.Pro20= (c.60T>C) in the general population?

TGM1 p.Pro20= (c.60T>C) is ultra-rare (popmax 0.0506%, afr) (gnomAD).

TGM1 p.Pro20=

c.60T>C · rs145812304 · VCV751266

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0506%, afr)

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 -0.76	GERP -3.1
Overall
CADD	0.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0506% African / African-American · 38/75,054 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00254% 41/1,613,684 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0506%	1,975
Admixed American	0.005%	20,011

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.Pro20=
Coding: c.60T>C
MANE Select: NM_000359
dbSNP: rs145812304
Type: single nucleotide variant
Location: chr14:24262293 (GRCh38)
Gene constraint: LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.04 · 1 PDB
Residue 20: the 'membrane anchorage region' region; the 'disordered' region

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-pro20 (accessed [today's date]).

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