Is GDA p.Ile229Phe (c.685A>T) pathogenic?

GDA p.Ile229Phe (c.685A>T) is classified Uncertain significance in GDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.139); Ultra-rare (popmax 0.0167%, amr).

How common is GDA p.Ile229Phe (c.685A>T) in the general population?

GDA p.Ile229Phe (c.685A>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about GDA p.Ile229Phe (c.685A>T)?

AlphaMissense predicts likely benign (score 0.139) — an in-silico prediction, not a clinical call.

GDA p.Ile229Phe

c.685A>T · VCV3281090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.139	likely benign
REVEL	0.577	indeterminate
SaProt	LLR -8.62	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 2	GERP -2.3, phastCons 0.61
Overall
CADD	18.84	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 0.0167% Admixed American · 10/59,964 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.000868% 14/1,612,358 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,996
European (non-Finnish)	0.000339%	294,652

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.Ile229Phe
Coding: c.685A>T
MANE Select: NM_004293
Type: single nucleotide variant
Location: chr9:72223198 (GRCh38)
Structure: AlphaFold pLDDT 85.09

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

Similar variants

GDA p.Ile229Thr Uncertain significance ★ ⚠ same residue
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

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-ile229phe (accessed [today's date]).

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