Is ALG3 p.Gln16Ter (c.46C>T) pathogenic?

ALG3 p.Gln16Ter (c.46C>T) is classified Likely pathogenic in ALG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). Ultra-rare (popmax 0.0167%, mid).

How common is ALG3 p.Gln16Ter (c.46C>T) in the general population?

ALG3 p.Gln16Ter (c.46C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

ALG3 p.Gln16Ter

c.46C>T · VCV4882593

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.22, phastCons 0.94
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,984 alleles

Filtering AF 0.000248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000499% 8/1,601,946 alleles · ultra-rare exomes 8/1,449,626 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,984
European (non-Finnish)	0.000596%	167,844

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.Gln16Ter
Coding: c.46C>T
MANE Select: NM_005787
Type: single nucleotide variant
Location: chr3:184248895 (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

Similar variants

ALG3 p.Gly16Trp Conflicting classifications of pathogenicity ★ same residue
ALG3 p.Gln16fs Pathogenic ★ same residue
ALG3 c.444+1G>T Likely pathogenic ★★ same type
ALG3 p.Arg171Gln Pathogenic/Likely pathogenic ★★ same type
ALG3 p.Arg266Cys Pathogenic ★★ same type
ALG3 p.Arg354Cys Likely pathogenic ★★ same type
ALG3 p.Arg354His Pathogenic/Likely pathogenic ★★ same type
ALG3 p.Asn174Ser Likely pathogenic ★★ ⚠ 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/alg3-p-gln16ter (accessed [today's date]).

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