Is ALG2 p.Tyr320= (c.960C>T) pathogenic?

ALG2 p.Tyr320= (c.960C>T) is classified Likely benign in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-09). Very rare (popmax 0.000254%, nfe).

How common is ALG2 p.Tyr320= (c.960C>T) in the general population?

ALG2 p.Tyr320= (c.960C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

ALG2 p.Tyr320=

c.960C>T · rs1588618745 · VCV738549

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 3.2	GERP -1.3, phastCons 1
Overall
CADD	6.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,056 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,260 alleles · very rare exomes 3/1,461,890 · genomes 0/152,370 · joint denominator

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.Tyr320=
Coding: c.960C>T
MANE Select: NM_033087
dbSNP: rs1588618745
Type: single nucleotide variant
Location: chr9:99218225 (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 p.Tyr320Cys Uncertain significance ★ ⚠ same residue
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

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-tyr320 (accessed [today's date]).

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