Is TGM1 p.Ser7= (c.21C>T) pathogenic?

TGM1 p.Ser7= (c.21C>T) is classified Likely benign in TGM1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-21). Very rare (popmax 0.005%, amr); Associated with autosomal recessive congenital ichthyosis 1.

What condition is associated with TGM1 p.Ser7= (c.21C>T)?

TGM1 p.Ser7= (c.21C>T) is associated with autosomal recessive congenital ichthyosis 1 (ClinVar).

How common is TGM1 p.Ser7= (c.21C>T) in the general population?

TGM1 p.Ser7= (c.21C>T) is very rare (popmax 0.005%, amr) (gnomAD).

TGM1 p.Ser7=

c.21C>T · rs150913268 · VCV766639

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

autosomal recessive congenital ichthyosis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -7.7	GERP -3.6
Overall
CADD	3.563	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,032 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00297% 48/1,613,604 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Admixed Americangrpmax	0.005%	20,011
European (non-Finnish)	0.00271%	36,876
African / African-American	0.00267%	37,521
East Asian	0.00223%	44,874
South Asian	0.0011%	91,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser7=
Coding: c.21C>T
MANE Select: NM_000359
dbSNP: rs150913268
Type: single nucleotide variant
Location: chr14:24262332 (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 7: 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-ser7 (accessed [today's date]).

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