Is ARSG p.Arg233His (c.698G>A) pathogenic?

ARSG p.Arg233His (c.698G>A) is classified Conflicting classifications of pathogenicity in ARSG (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-20). AlphaMissense: likely benign (0.0577); Ultra-rare (popmax 0.0493%, mid).

How common is ARSG p.Arg233His (c.698G>A) in the general population?

ARSG p.Arg233His (c.698G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about ARSG p.Arg233His (c.698G>A)?

AlphaMissense predicts likely benign (score 0.0577) — an in-silico prediction, not a clinical call.

ARSG p.Arg233His

c.698G>A · rs774988063 · VCV1054855

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0577 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0577	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.69	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 0.34	GERP -0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 113 kb · p 0.075 · regional, not allelic
Overall
CADD	14.38	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00124% 20/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
East Asian	0.0111%	8,976
Admixed American	0.00667%	15,002
African / African-American	0.004%	24,971
European (non-Finnish)	0.000424%	236,005

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: ARSG
Protein: p.Arg233His
Coding: c.698G>A
MANE Select: NM_001267727
dbSNP: rs774988063
Type: single nucleotide variant
Location: chr17:68356798 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90

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

Similar variants

ARSG p.Arg233Cys Uncertain significance ★★ ⚠ same residue
ARSG p.Arg233Leu Uncertain significance ★ ⚠ same residue
ARSG c.1091+1G>A Likely pathogenic ★★ same type
ARSG c.982+2T>G Likely pathogenic ★★ same type
ARSG p.Ala180Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala262Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala313Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala374Pro 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/arsg-p-arg233his (accessed [today's date]).

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