Is ALG1 c.629+166G>A pathogenic?

ALG1 c.629+166G>A is classified Likely benign in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-28). Low-frequency (popmax 3.87%, sas).

How common is ALG1 c.629+166G>A in the general population?

ALG1 c.629+166G>A is low-frequency (popmax 3.87%, sas) (gnomAD).

ALG1 c.629+166G>A

rs116891668 · VCV1192832

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.87%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +166	deep intronic (+166 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -2.4
Overall
CADD	0.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.87% South Asian · 187/4,828 alleles

Filtering AF 3.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.24%

Overall 1.46% 2,224/152,304 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.15%	19
South Asiangrpmax	3.87%	26
Finnishnot grpmax-eligible	2.38%	42
European (non-Finnish)	2.04%	49
Ashkenazi Jewishnot grpmax-eligible	2.02%	50
Middle Eastern	1.7%	59
Remaining individualsnot grpmax-eligible	1.28%	78
Admixed American	0.647%	155
African / African-American	0.346%	289
East Asian	0.0386%	2,594

Amish 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: ALG1
Coding: c.629+166G>A
MANE Select: NM_019109
dbSNP: rs116891668
Type: single nucleotide variant
Location: chr16:5077700 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same type
ALG1 c.1187+2T>C Pathogenic ★★ same type
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same type
ALG1 c.209-2A>G Likely pathogenic ★★ same type
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same type
ALG1 c.630-2A>G Likely pathogenic ★★ same type
ALG1 c.863-2A>G Likely pathogenic ★★ same type
ALG1 c.961+1G>A 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/alg1-c-629-plus-166g-a (accessed [today's date]).

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