Is GUSB p.Phe319Ser (c.956T>C) pathogenic?

GUSB p.Phe319Ser (c.956T>C) is classified Uncertain significance in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-18). AlphaMissense: likely benign (0.16); Absent from gnomAD v4.1.

How common is GUSB p.Phe319Ser (c.956T>C) in the general population?

GUSB p.Phe319Ser (c.956T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GUSB p.Phe319Ser (c.956T>C)?

AlphaMissense predicts likely benign (score 0.16) — an in-silico prediction, not a clinical call.

GUSB p.Phe319Ser

c.956T>C · rs2115961823 · VCV1343444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.16 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.16	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.55, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 15 kb · p 3.7e-08 · regional, not allelic
Overall
CADD	19.06	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: GUSB
Protein: p.Phe319Ser
Coding: c.956T>C
MANE Select: NM_000181
dbSNP: rs2115961823
Type: single nucleotide variant
Location: chr7:65975028 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 319: a β-strand

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

Similar variants

GUSB p.Phe319Leu Uncertain significance ★ ⚠ same residue
GUSB c.1244+1G>A Pathogenic ★★ same type
GUSB c.581+1G>A Pathogenic/Likely pathogenic ★★ same type
GUSB c.724+1G>T Pathogenic/Likely pathogenic ★★ same type
GUSB p.Ala619Val Pathogenic/Likely pathogenic ★★ same type
GUSB p.Arg110Ter Pathogenic/Likely pathogenic ★★ same type
GUSB p.Arg167Ter Pathogenic/Likely pathogenic ★★ same type
GUSB p.Arg216Trp Pathogenic/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/gusb-p-phe319ser (accessed [today's date]).

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