Is GDA p.Val290Ile (c.868G>A) pathogenic?

GDA p.Val290Ile (c.868G>A) is classified Uncertain significance in GDA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0713); Ultra-rare (popmax 0.0254%, afr).

How common is GDA p.Val290Ile (c.868G>A) in the general population?

GDA p.Val290Ile (c.868G>A) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about GDA p.Val290Ile (c.868G>A)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

GDA p.Val290Ile

c.868G>A · VCV4262720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -3.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -5.4
Overall
CADD	0.344	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

Grpmax group 0.0254% African / African-American · 19/74,800 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00224% 36/1,609,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,937
Middle Eastern	0.0165%	6,076
Admixed American	0.00167%	59,906
European (non-Finnish)	0.00119%	84,003
South Asian	0.0011%	90,724

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GDA
Protein: p.Val290Ile
Coding: c.868G>A
MANE Select: NM_152707 · reported on NM_004293
Type: single nucleotide variant
Location: chr9:72227988 (GRCh38)
Structure: AlphaFold pLDDT 85.09

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

Similar variants

SLC25A16 p.Arg265Cys Likely pathogenic ★ same type
GDA c.*2442C>A Uncertain significance ★ same type
GDA c.*2458C>A Uncertain significance ★ same type
GDA p.Ala299Thr Uncertain significance ★ same type
GDA p.Arg14Gln Uncertain significance ★ ⚠ same type
GDA p.Arg233Cys Uncertain significance ★ ⚠ same type
GDA p.Arg435Gln Uncertain significance ★ ⚠ same type
GDA p.Asn289Lys 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/gda-p-val290ile (accessed [today's date]).

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