Is GLA p.Val316fs (c.946_947insACGACACATC…[47 bp]) pathogenic?

GLA p.Val316fs (c.946947insACGACACATC…[47 bp]) is classified Pathogenic in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-28). No gnomAD frequency available for this variant; Associated with Fabry disease.

What condition is associated with GLA p.Val316fs (c.946_947insACGACACATC…[47 bp])?

GLA p.Val316fs (c.946_947insACGACACATC…[47 bp]) is associated with Fabry disease (ClinVar).

How common is GLA p.Val316fs (c.946_947insACGACACATC…[47 bp]) in the general population?

GLA p.Val316fs (c.946_947insACGACACATC…[47 bp]) is no gnomAD frequency available for this variant (gnomAD).

How is Fabry disease inherited?

Typically X-linked dominant, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GLA p.Val316fs

c.946_947insACGACACATC…[47 bp] · rs2147471979 · VCV1308629

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fabry disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 3.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GLA
Protein: p.Val316fs
Coding: c.946_947insACGACACATCAGCCCTCAAGCCAAAGCTCTCCTTCAGGATAAGGACG
MANE Select: NM_000169
dbSNP: rs2147471979
Type: Insertion
Location: chrX:101398422 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 316: a UniProt-annotated variant site (in fabryd); a UniProt-annotated variant site (in fabryd; uncertain significance; decreased enzyme activity); an α-helix

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

Disease context

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

For Fabry disease (Orphanet):

Inheritance: X-linked dominant, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

GLA p.Val316Ala Uncertain significance ★★ ⚠ same residue
GLA p.Val316Ile Uncertain significance ★★ ⚠ same residue
GLA p.Val316_Asp322del Likely pathogenic ★ same residue
GLA p.Val316Glu Likely pathogenic ★ same residue
GLA p.Val316Gly Likely pathogenic ★ same residue
GLA p.Arg49_Phe50insPro Likely pathogenic ★ same condition
GLA p.Asn298fs Pathogenic ★ same condition
GLA p.Asp155fs Pathogenic ★ 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/gla-p-val316fs (accessed [today's date]).

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