Is ASPH p.Arg598Gln (c.1793G>A) pathogenic?

ASPH p.Arg598Gln (c.1793G>A) is classified Uncertain significance in ASPH (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.3127); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with ASPH p.Arg598Gln (c.1793G>A)?

ASPH p.Arg598Gln (c.1793G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASPH p.Arg598Gln (c.1793G>A) in the general population?

ASPH p.Arg598Gln (c.1793G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about ASPH p.Arg598Gln (c.1793G>A)?

AlphaMissense predicts likely benign (score 0.3127) — an in-silico prediction, not a clinical call.

ASPH p.Arg598Gln

c.1793G>A · rs375445620 · VCV2391650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3127 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3127	likely benign
REVEL	0.54	indeterminate
SaProt	LLR -10.83	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 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 211 kb · p 0.99 · regional, not allelic
Overall
CADD	28.8	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 0.0117% Admixed American · 7/59,990 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00483% 78/1,613,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,570
European (non-Finnish)	0.00559%	17,878
Remaining individualsnot grpmax-eligible	0.0048%	20,824
East Asian	0.00223%	44,892
South Asian	0.0011%	91,080

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: ASPH
Protein: p.Arg598Gln
Coding: c.1793G>A
MANE Select: NM_004318
dbSNP: rs375445620
Type: single nucleotide variant
Location: chr8:61526084 (GRCh38)
Gene constraint: LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 43 PDB
Residue 598: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASPH p.Arg753His Uncertain significance ★★ ⚠ same condition
ASPH p.Glu506Val Uncertain significance ★★ ⚠ same condition
ASPH p.Leu433Arg Uncertain significance ★★ ⚠ same condition
ASPH p.Ser299Asn Uncertain significance ★★ ⚠ same condition
ASPH p.Val214Met Uncertain significance ★★ ⚠ same condition
ASPH p.Val462Met Uncertain significance ★★ ⚠ same condition
ASPH p.Val83Ala Uncertain significance ★★ ⚠ same condition
ASPH p.Met188Thr Likely benign ★★ same condition

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/asph-p-arg598gln (accessed [today's date]).

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