Is ASMT p.Trp190Arg (c.568T>C) pathogenic?

ASMT p.Trp190Arg (c.568T>C) is classified Benign in ASMT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-22). Common (popmax 54.5%, mid) — too common for a highly-penetrant pathogenic allele; Associated with ASMT-related disorder.

What condition is associated with ASMT p.Trp190Arg (c.568T>C)?

ASMT p.Trp190Arg (c.568T>C) is associated with ASMT-related disorder (ClinVar).

ASMT p.Trp190Arg

Q: How common is ASMT p.Trp190Arg (c.568T>C) in the general population?

ASMT p.Trp190Arg (c.568T>C) is common (popmax 54.5%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.568T>C · rs6588809 · VCV3036492

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 54.5%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

ASMT-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP 0.14, phastCons 0.009
Regional constraint	o/e 1.20	unconstrained · MANE · 28 kb · p 2e-05 · regional, not allelic
Overall
CADD	8.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 54.5% Middle Eastern · 329/604 alleles

Filtering AF 49.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.1%

Overall 44.3% 108,028/243,960 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	57.4%	2
Middle Easterngrpmax	54.5%	2
South Asian	49.3%	2
Remaining individualsnot grpmax-eligible	46.2%	2
East Asian	45.9%	2
European (non-Finnish)	44.8%	2
Amishnot grpmax-eligible	43.6%	2
Admixed American	43.4%	2
African / African-American	41.9%	2
Finnishnot grpmax-eligible	34.8%	3

Ashkenazi Jewish 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: ASMT
Protein: p.Trp190Arg
Coding: c.568T>C
MANE Select: NM_001171038
dbSNP: rs6588809
Type: single nucleotide variant
Location: chrX:1632709 (GRCh38)
Structure: AlphaFold pLDDT 95.55 · 2 PDB

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

Disease context

ASMT-related disorder

Similar variants

ASMT p.Arg210= Likely benign same condition
ASMT p.Asp122= Likely benign same condition
ASMT p.Asp287= Benign same condition
ASMT c.910+8del Likely benign same condition
ASMT p.Lys81Glu Likely benign ★★ same type
ASMT c.562+2T>C Conflicting classifications of pathogenicity ★ same type
ASMT p.Asn17Lys Uncertain significance ★ same type
ASMT p.Cys29Ter Uncertain significance ★ 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/asmt-p-trp190arg (accessed [today's date]).

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