Is ALG3 p.Val415Ile (c.1243G>A) pathogenic?

ALG3 p.Val415Ile (c.1243G>A) is classified Uncertain significance in ALG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0751); Ultra-rare (popmax 0.0156%, sas); Associated with Inborn genetic diseases.

What condition is associated with ALG3 p.Val415Ile (c.1243G>A)?

ALG3 p.Val415Ile (c.1243G>A) is associated with Inborn genetic diseases, ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Val415Ile (c.1243G>A) in the general population?

ALG3 p.Val415Ile (c.1243G>A) is ultra-rare (popmax 0.0156%, sas) (gnomAD).

What do computational predictors say about ALG3 p.Val415Ile (c.1243G>A)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

ALG3 p.Val415Ile

c.1243G>A · rs375976807 · VCV962232

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -6.37	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 -0.085	GERP 0.65
Regional constraint	o/e 0.82	unconstrained · MANE · 2,165 bp · p 0.0031 · regional, not allelic
Overall
CADD	11.13	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 0.0156% South Asian · 14/90,010 alleles

Filtering AF 0.0094% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00753%

Overall 0.00574% 92/1,604,084 alleles · ultra-rare exomes 81/1,451,916 · genomes 11/152,168 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0156%	6,429
African / African-American	0.00669%	14,950
European (non-Finnish)	0.00563%	17,777
Admixed American	0.00503%	19,880
East Asian	0.00447%	22,362
Remaining individualsnot grpmax-eligible	0.00322%	31,013

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.Val415Ile
Coding: c.1243G>A
MANE Select: NM_005787
dbSNP: rs375976807
Type: single nucleotide variant
Location: chr3:184242588 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG3-congenital disorder of glycosylation

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-val415ile (accessed [today's date]).

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