Is ALG3 p.Val339Ile (c.1015G>A) pathogenic?

ALG3 p.Val339Ile (c.1015G>A) is classified Uncertain significance in ALG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.0825); Very rare (popmax 0.00445%, eas); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Val339Ile (c.1015G>A)?

ALG3 p.Val339Ile (c.1015G>A) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Val339Ile (c.1015G>A) in the general population?

ALG3 p.Val339Ile (c.1015G>A) is very rare (popmax 0.00445%, eas) (gnomAD).

How is ALG3-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG3 p.Val339Ile (c.1015G>A)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

ALG3 p.Val339Ile

c.1015G>A · rs1323127252 · VCV900789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 2,165 bp · p 0.0031 · regional, not allelic
Overall
CADD	17.8	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 0.00445% East Asian · 2/44,898 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000806% 13/1,613,158 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,449
South Asian	0.0011%	91,032
European (non-Finnish)	0.000848%	117,977

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: ALG3
Protein: p.Val339Ile
Coding: c.1015G>A
MANE Select: NM_005787
dbSNP: rs1323127252
Type: single nucleotide variant
Location: chr3:184242952 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG3-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG3 c.444+1G>T Likely pathogenic ★★ same condition
ALG3 p.Arg171Gln Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Arg266Cys Pathogenic ★★ same condition
ALG3 p.Arg354Cys Likely pathogenic ★★ same condition
ALG3 p.Arg354His Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Asn174Ser Likely pathogenic ★★ ⚠ same condition
ALG3 p.Gly55= Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Ile69Thr Likely 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/alg3-p-val339ile (accessed [today's date]).

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