Is ASPH p.Arg429Gly (c.1285A>G) pathogenic?

ASPH p.Arg429Gly (c.1285A>G) is classified Uncertain significance in ASPH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely pathogenic (0.9791); Absent from gnomAD v4.1.

How common is ASPH p.Arg429Gly (c.1285A>G) in the general population?

ASPH p.Arg429Gly (c.1285A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPH p.Arg429Gly (c.1285A>G)?

AlphaMissense predicts likely pathogenic (score 0.9791) — an in-silico prediction, not a clinical call.

ASPH p.Arg429Gly

c.1285A>G · VCV4775085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9791 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9791	likely pathogenic
REVEL	0.533	indeterminate
SaProt	LLR -15.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -3.5, phastCons 0.96
Regional constraint	o/e 1.00	unconstrained · MANE · 211 kb · p 0.99 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: ASPH
Protein: p.Arg429Gly
Coding: c.1285A>G
MANE Select: NM_004318
Type: single nucleotide variant
Location: chr8:61567183 (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 429: an α-helix

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

Similar variants

ASPH p.Arg735Trp Likely pathogenic ★★ same type
ASPH p.Tyr565Ter Pathogenic/Likely pathogenic ★★ same type
ASPH p.Arg425Cys Uncertain significance ★★ ⚠ same type
ASPH p.Arg753His Uncertain significance ★★ ⚠ same type
ASPH p.Glu506Val Uncertain significance ★★ ⚠ same type
ASPH p.Leu433Arg Uncertain significance ★★ ⚠ same type
ASPH p.Ser299Asn Uncertain significance ★★ ⚠ same type
ASPH p.Val214Met 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/asph-p-arg429gly (accessed [today's date]).

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