Is ARSL p.His165Gln (c.495T>G) pathogenic?

ARSL p.His165Gln (c.495T>G) is classified Benign in ARSL (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). AlphaMissense: likely pathogenic (0.5763); Absent from gnomAD v4.1.

How common is ARSL p.His165Gln (c.495T>G) in the general population?

ARSL p.His165Gln (c.495T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSL p.His165Gln (c.495T>G)?

AlphaMissense predicts likely pathogenic (score 0.5763) — an in-silico prediction, not a clinical call.

ARSL p.His165Gln

c.495T>G · rs35274634 · VCV157733

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5763	likely pathogenic
REVEL	0.528	indeterminate
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -3.1	GERP -3
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	6.04	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARSL
Protein: p.His165Gln
Coding: c.495T>G
MANE Select: NM_000047
dbSNP: rs35274634
Type: single nucleotide variant
Location: chrX:2949663 (GRCh38)
Structure: AlphaFold pLDDT 92.57

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

Similar variants

ARSL p.His165= Benign ★★ same residue
ARSL c.1289+1G>A Pathogenic/Likely pathogenic ★★ same type
ARSL c.24-2A>G Likely pathogenic ★★ same type
ARSL p.Arg111Cys Likely pathogenic ★★ same type
ARSL p.Gly117Arg Pathogenic/Likely pathogenic ★★ same type
ARSL p.Gly73Ser Likely pathogenic ★★ ⚠ same type
ARSL p.Ala182Thr Uncertain significance ★★ ⚠ same type
ARSL p.Ala251Val 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/arsl-p-his165gln (accessed [today's date]).

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