Is ARSH p.Thr64= (c.192C>T) pathogenic?

ARSH p.Thr64= (c.192C>T) is classified Benign in ARSH (ClinVar, Single submitter, 2 submitters). Common (popmax 11.8%, nfe) — too common for a highly-penetrant pathogenic allele.

ARSH p.Thr64=

Q: How common is ARSH p.Thr64= (c.192C>T) in the general population?

ARSH p.Thr64= (c.192C>T) is common (popmax 11.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.192C>T · rs77183343 · VCV558977

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 11.8%, nfe) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.1
Overall
CADD	0.304	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.8% European (non-Finnish) · 105,287/894,474 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.7%

Overall 10.6% 128,689/1,208,646 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	11.8%	8
African / African-American	10.3%	10
Remaining individualsnot grpmax-eligible	10.3%	10
Finnishnot grpmax-eligible	9.41%	11
Middle Eastern	9.2%	11
Ashkenazi Jewishnot grpmax-eligible	7.59%	13
South Asian	7.41%	14
Amishnot grpmax-eligible	5.6%	18
Admixed American	3.92%	26
East Asian	0.53%	189

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: ARSH
Protein: p.Thr64=
Coding: c.192C>T
MANE Select: NM_001011719
dbSNP: rs77183343
Type: single nucleotide variant
Location: chrX:3010129 (GRCh38)
Structure: AlphaFold pLDDT 94.15

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

Similar variants

ARSH p.Arg358Cys Benign ★★ ⚠ same type
ARSH p.Arg37His Benign ★★ ⚠ same type
ARSH p.Met408Ile Benign ★★ same type
ARSH p.Pro144Thr Benign ★★ ⚠ same type
ARSH p.Ala100Thr Uncertain significance ★ ⚠ same type
ARSH p.Ala14Thr Uncertain significance ★ ⚠ same type
ARSH p.Ala175Val Uncertain significance ★ ⚠ same type
ARSH p.Ala187Thr 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/arsh-p-thr64 (accessed [today's date]).

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