Is ASNS p.Ala129Pro (c.385G>C) pathogenic?

ASNS p.Ala129Pro (c.385G>C) is classified Uncertain significance in ASNS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: ambiguous (0.3615); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASNS p.Ala129Pro (c.385G>C)?

ASNS p.Ala129Pro (c.385G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASNS p.Ala129Pro (c.385G>C) in the general population?

ASNS p.Ala129Pro (c.385G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASNS p.Ala129Pro (c.385G>C)?

AlphaMissense predicts ambiguous (score 0.3615) — an in-silico prediction, not a clinical call.

ASNS p.Ala129Pro

c.385G>C · rs2484682319 · VCV3130397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3615 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3615	ambiguous
REVEL	0.189	benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.32, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	23.9	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: ASNS
Protein: p.Ala129Pro
Coding: c.385G>C
MANE Select: NM_001673
dbSNP: rs2484682319
Type: single nucleotide variant
Location: chr7:97864361 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 129: the glutamine amidotransferase type-2 domain; a turn

Full ASNS 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

ASNS c.1320+1G>C Likely pathogenic ★★ same condition
ASNS p.Arg465Ter Pathogenic/Likely pathogenic ★★ same condition
ASNS p.Arg550His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ASNS c.1238+3A>G Uncertain significance ★★ same condition
ASNS p.Ala303Glu Uncertain significance ★★ ⚠ same condition
ASNS p.Arg251Gly Uncertain significance ★★ ⚠ same condition
ASNS p.Arg392Lys Uncertain significance ★★ ⚠ same condition
ASNS p.Asn441Ser Uncertain significance ★★ ⚠ 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/asns-p-ala129pro (accessed [today's date]).

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