Is TMLHE p.Phe191= (c.573C>T) pathogenic?

TMLHE p.Phe191= (c.573C>T) is classified Benign in TMLHE (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-14). Rare (popmax 0.31%, nfe).

How common is TMLHE p.Phe191= (c.573C>T) in the general population?

TMLHE p.Phe191= (c.573C>T) is rare (popmax 0.31%, nfe) (gnomAD).

TMLHE p.Phe191=

c.573C>T · rs145115289 · VCV720856

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.31%, nfe)

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 3.2	GERP -0.19, phastCons 1
Overall
CADD	6.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.31% European (non-Finnish) · 2,770/894,559 alleles

Filtering AF 0.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.296%

Overall 0.251% 3,029/1,208,930 alleles · rare exomes 2,849/1,097,308 · genomes 180/111,622 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.333%	300
European (non-Finnish)grpmax	0.31%	323
Remaining individualsnot grpmax-eligible	0.137%	732
Admixed American	0.0416%	2,401
African / African-American	0.028%	3,570
South Asian	0.00528%	18,925
East Asian	0.00296%	33,728

Finnish 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: TMLHE
Protein: p.Phe191=
Coding: c.573C>T
MANE Select: NM_018196
dbSNP: rs145115289
Type: single nucleotide variant
Location: chrX:155514051 (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-phe191 (accessed [today's date]).

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