Is GAA p.Val867= (c.2601G>T) pathogenic?

GAA p.Val867= (c.2601G>T) is classified Likely benign in GAA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-07). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Val867= (c.2601G>T)?

GAA p.Val867= (c.2601G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is GAA p.Val867= (c.2601G>T) in the general population?

GAA p.Val867= (c.2601G>T) is absent from gnomAD v4.1 (gnomAD).

GAA p.Val867=

c.2601G>T · VCV4825883

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP 1.7, phastCons 0.005
Overall
CADD	3.451	PHRED · no single calibrated threshold — expert panels disagree

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: GAA
Protein: p.Val867=
Coding: c.2601G>T
MANE Select: NM_000152
Type: single nucleotide variant
Location: chr17:80118312 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 867: an α-helix

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

Disease context

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

Similar variants

GAA p.Val867Leu Uncertain significance ★ ⚠ same residue
GAA c.2646+1G>A Pathogenic/Likely pathogenic ★★ same condition
GAA p.Arg190His Pathogenic/Likely pathogenic ★★ same condition
GAA c.546+3G>A Uncertain significance ★★ same condition
GAA p.Ala24Thr Uncertain significance ★★ ⚠ same condition
GAA p.Ala625Thr Uncertain significance ★★ ⚠ same condition
GAA p.Ala719Val Uncertain significance ★★ ⚠ same condition
GAA p.Arg870Pro Uncertain significance ★★ ⚠ 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/gaa-p-val867 (accessed [today's date]).

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