Is ALG2 p.Gly57= (c.171C>A) pathogenic?

ALG2 p.Gly57= (c.171C>A) is classified Likely benign in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-02). Ultra-rare (popmax 0.022%, sas).

How common is ALG2 p.Gly57= (c.171C>A) in the general population?

ALG2 p.Gly57= (c.171C>A) is ultra-rare (popmax 0.022%, sas) (gnomAD).

ALG2 p.Gly57=

c.171C>A · rs778702945 · VCV799656

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	phastCons 1
Overall
CADD	13.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% South Asian · 20/90,862 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00125% 20/1,597,894 alleles · ultra-rare

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: ALG2
Protein: p.Gly57=
Coding: c.171C>A
MANE Select: NM_033087
dbSNP: rs778702945
Type: single nucleotide variant
Location: chr9:99221724 (GRCh38)
Gene constraint: LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.03

Full ALG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG2 c.348+568G>A Uncertain significance ★★ same type
ALG2 p.Ala29Pro Uncertain significance ★★ ⚠ same type
ALG2 p.Ala36Val Uncertain significance ★★ ⚠ same type
ALG2 p.Ala71Gly Uncertain significance ★★ ⚠ same type
ALG2 p.Ala71Val Uncertain significance ★★ ⚠ same type
ALG2 p.Arg129Gln Uncertain significance ★★ ⚠ same type
ALG2 p.Arg130Gln Uncertain significance ★★ ⚠ same type
ALG2 p.Arg251His Uncertain significance ★★ ⚠ 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/alg2-p-gly57 (accessed [today's date]).

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