Is TMLHE p.Val100= (c.300G>T) pathogenic?

TMLHE p.Val100= (c.300G>T) is classified Likely benign in TMLHE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-12). Very rare (popmax 0.00179%, sas).

How common is TMLHE p.Val100= (c.300G>T) in the general population?

TMLHE p.Val100= (c.300G>T) is very rare (popmax 0.00179%, sas) (gnomAD).

TMLHE p.Val100=

c.300G>T · VCV4953803

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00179%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.17	GERP 0.69, phastCons 0.78
Overall
CADD	4.646	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00179% South Asian · 1/55,943 alleles

Overall 8.28e-05% 1/1,207,998 alleles · very rare exomes 1/1,094,507 · genomes 0/113,491 · 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: TMLHE
Protein: p.Val100=
Coding: c.300G>T
MANE Select: NM_018196
Type: single nucleotide variant
Location: chrX:155524514 (GRCh38)
Structure: AlphaFold pLDDT 89.10

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

Similar variants

TMLHE p.Arg77Ter Uncertain significance ★★ same type
TMLHE p.Arg93His Uncertain significance ★★ ⚠ same type
TMLHE p.Glu175Lys Uncertain significance ★★ ⚠ same type
TMLHE p.Glu369Asp Uncertain significance ★★ ⚠ same type
TMLHE p.Pro29Ala Uncertain significance ★★ ⚠ same type
TMLHE p.Thr265Ile Uncertain significance ★★ ⚠ same type
TMLHE p.Trp53Ter Uncertain significance ★★ same type
TMLHE p.Gly266= Likely benign ★★ 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/tmlhe-p-val100 (accessed [today's date]).

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