Is ASNS p.Pro61Leu (c.182C>T) pathogenic?

ASNS p.Pro61Leu (c.182C>T) is classified Pathogenic in ASNS (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.975); Very rare (popmax 0.000169%, nfe); Associated with Neurodevelopmental delay.

What condition is associated with ASNS p.Pro61Leu (c.182C>T)?

ASNS p.Pro61Leu (c.182C>T) is associated with Neurodevelopmental delay (ClinVar).

How common is ASNS p.Pro61Leu (c.182C>T) in the general population?

ASNS p.Pro61Leu (c.182C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ASNS p.Pro61Leu (c.182C>T)?

AlphaMissense predicts likely pathogenic (score 0.975) — an in-silico prediction, not a clinical call.

ASNS p.Pro61Leu

c.182C>T · rs2115753664 · VCV1700067

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Neurodevelopmental delay

Computational evidence

Protein change
AlphaMissense	0.975	likely pathogenic ✓ concordant with ClinVar
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -8.74	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	31.0	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 0.000169% European (non-Finnish) · 2/1,180,034 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,882 alleles · very rare

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: ASNS
Protein: p.Pro61Leu
Coding: c.182C>T
MANE Select: NM_001673
dbSNP: rs2115753664
Type: single nucleotide variant
Location: chr7:97868975 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 61: the glutamine amidotransferase type-2 domain; a β-strand

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

Disease context

Neurodevelopmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASNS c.1030+1G>A Likely pathogenic ★★ same type
ASNS c.1138-1G>A Likely pathogenic ★★ same type
ASNS c.1239-2A>T Likely pathogenic ★★ same type
ASNS c.1320+1G>C Likely pathogenic ★★ same type
ASNS c.1320+1G>T Likely pathogenic ★★ same type
ASNS c.1321-1G>A Likely pathogenic ★★ same type
ASNS c.1476+1G>A Pathogenic ★★ same type
ASNS c.1476+2T>C Likely pathogenic ★★ 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/asns-p-pro61leu (accessed [today's date]).

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