Is ASPG p.Val319Phe (c.955G>T) pathogenic?

ASPG p.Val319Phe (c.955G>T) is classified Uncertain significance in ASPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1364); Absent from gnomAD v4.1.

How common is ASPG p.Val319Phe (c.955G>T) in the general population?

ASPG p.Val319Phe (c.955G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPG p.Val319Phe (c.955G>T)?

AlphaMissense predicts likely benign (score 0.1364) — an in-silico prediction, not a clinical call.

ASPG p.Val319Phe

c.955G>T · VCV4155550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1364 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1364	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -11.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.1, phastCons 0.023
Regional constraint	o/e 0.93	unconstrained · MANE · 27 kb · p 0.058 · regional, not allelic
Overall
CADD	16.43	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: ASPG
Protein: p.Val319Phe
Coding: c.955G>T
MANE Select: NM_001080464
Type: single nucleotide variant
Location: chr14:104104640 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 2 PDB
Residue 319: the asparaginase/glutaminase domain; the 'asparaginase' region

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

Similar variants

ASPG p.Asp223= Benign ★★ same type
ASPG c.1620+1G>A Uncertain significance ★ same type
ASPG p.Ala315Gly Uncertain significance ★ ⚠ same type
ASPG p.Ala315Val Uncertain significance ★ ⚠ same type
ASPG p.Ala332Val Uncertain significance ★ ⚠ same type
ASPG p.Ala442Thr Uncertain significance ★ ⚠ same type
ASPG p.Ala4Thr Uncertain significance ★ ⚠ same type
ASPG p.Ala537Ser 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/aspg-p-val319phe (accessed [today's date]).

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