Is ASNS p.Phe123Ser (c.368T>C) pathogenic?

ASNS p.Phe123Ser (c.368T>C) is classified Uncertain significance in ASNS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely pathogenic (0.9313); Absent from gnomAD v4.1.

How common is ASNS p.Phe123Ser (c.368T>C) in the general population?

ASNS p.Phe123Ser (c.368T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASNS p.Phe123Ser (c.368T>C)?

AlphaMissense predicts likely pathogenic (score 0.9313) — an in-silico prediction, not a clinical call.

ASNS p.Phe123Ser

c.368T>C · VCV3385188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9313 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9313	likely pathogenic
REVEL	0.647	pathogenic-leaning
SaProt	LLR -16.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, 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

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: ASNS
Protein: p.Phe123Ser
Coding: c.368T>C
MANE Select: NM_001673
Type: single nucleotide variant
Location: chr7:97864378 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 123: the glutamine amidotransferase type-2 domain; a β-strand

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

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-phe123ser (accessed [today's date]).

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