Is ALG3 c.52+196G>T pathogenic?

ALG3 c.52+196G>T is classified Likely benign in ALG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-02-13). Low-frequency (popmax 2.36%, nfe).

How common is ALG3 c.52+196G>T in the general population?

ALG3 c.52+196G>T is low-frequency (popmax 2.36%, nfe) (gnomAD).

ALG3 c.52+196G>T

rs2233462 · VCV1189741

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.36%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.092	moderately benign-leaning
Splicing
Splice region	donor +196	deep intronic (+196 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -3.3
Non-coding constraint	Z 3.04	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	2.944	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.36% European (non-Finnish) · 26,836/1,136,686 alleles

Filtering AF 2.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.33%

Overall 1.98% 30,348/1,532,356 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.26%	31
European (non-Finnish)grpmax	2.36%	42
Amishnot grpmax-eligible	2.19%	46
Remaining individualsnot grpmax-eligible	1.51%	66
Admixed American	0.745%	134
African / African-American	0.343%	292
Middle Eastern	0.335%	299
Ashkenazi Jewishnot grpmax-eligible	0.287%	349
South Asian	0.204%	491
East Asian	0.00489%	20,440

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.52+196G>T
MANE Select: NM_005787 · reported on NM_001006941
dbSNP: rs2233462
Type: single nucleotide variant
Location: chr3:184249030 (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 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
ALG3 p.Gly55= Pathogenic/Likely pathogenic ★★ same type
ALG3 p.Ile69Thr 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-c-52-plus-196g-t (accessed [today's date]).

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