Is ARSH p.Arg188His (c.563G>A) pathogenic?

ARSH p.Arg188His (c.563G>A) is classified Likely benign in ARSH (ClinVar, Single submitter, 2 submitters). AlphaMissense: likely benign (0.0871); Low-frequency (popmax 1.76%, nfe).

How common is ARSH p.Arg188His (c.563G>A) in the general population?

ARSH p.Arg188His (c.563G>A) is low-frequency (popmax 1.76%, nfe) (gnomAD).

What do computational predictors say about ARSH p.Arg188His (c.563G>A)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

ARSH p.Arg188His

c.563G>A · rs142811205 · VCV558982

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.76%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -2.5
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.56 · regional, not allelic
Overall
CADD	7.249	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.76% European (non-Finnish) · 15,741/894,276 alleles

Filtering AF 1.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.73%

Overall 1.49% 17,995/1,207,986 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.76%	57
Middle Eastern	1.68%	60
Remaining individualsnot grpmax-eligible	1.39%	72
Ashkenazi Jewishnot grpmax-eligible	1.17%	85
South Asian	1.06%	95
Finnishnot grpmax-eligible	0.697%	143
Amishnot grpmax-eligible	0.583%	172
Admixed American	0.506%	198
African / African-American	0.189%	528
East Asian	0.00297%	33,707

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.Arg188His
Coding: c.563G>A
MANE Select: NM_001011719
dbSNP: rs142811205
Type: single nucleotide variant
Location: chrX:3015192 (GRCh38)
Structure: AlphaFold pLDDT 94.15

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

Similar variants

ARSH p.Arg188Cys Uncertain significance ★ ⚠ same residue
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

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-arg188his (accessed [today's date]).

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