Is ARSH p.Val143Gly (c.428T>G) pathogenic?

ARSH p.Val143Gly (c.428T>G) is classified Likely benign in ARSH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-05-17). AlphaMissense: likely benign (0.146); Rare (popmax 0.806%, afr).

How common is ARSH p.Val143Gly (c.428T>G) in the general population?

ARSH p.Val143Gly (c.428T>G) is rare (popmax 0.806%, afr) (gnomAD).

What do computational predictors say about ARSH p.Val143Gly (c.428T>G)?

AlphaMissense predicts likely benign (score 0.146) — an in-silico prediction, not a clinical call.

ARSH p.Val143Gly

c.428T>G · rs143533816 · VCV558981

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.146 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.806%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.146	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -11.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP 0.6
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.56 · regional, not allelic
Overall
CADD	14.05	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 0.806% African / African-American · 459/56,977 alleles

Filtering AF 0.745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.721%

Overall 0.0427% 516/1,208,884 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.806%	124
Admixed American	0.0593%	1,687
Remaining individualsnot grpmax-eligible	0.0567%	1,763
South Asian	0.0053%	18,859

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.Val143Gly
Coding: c.428T>G
MANE Select: NM_001011719
dbSNP: rs143533816
Type: single nucleotide variant
Location: chrX:3015057 (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-val143gly (accessed [today's date]).

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