Is ALG1 p.Leu312= (c.936T>A) pathogenic?

ALG1 p.Leu312= (c.936T>A) is classified Likely benign in ALG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-07-22). Very rare (popmax 0.00802%, afr); Associated with ALG1-related disorder.

What condition is associated with ALG1 p.Leu312= (c.936T>A)?

ALG1 p.Leu312= (c.936T>A) is associated with ALG1-related disorder (ClinVar).

How common is ALG1 p.Leu312= (c.936T>A) in the general population?

ALG1 p.Leu312= (c.936T>A) is very rare (popmax 0.00802%, afr) (gnomAD).

ALG1 p.Leu312=

c.936T>A · rs772979306 · VCV3036862

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00802%, afr)

Conditions

ALG1-related disorder

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 -0.51	GERP -3.6, phastCons 0.067
Overall
CADD	2.969	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00802% African / African-American · 6/74,832 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,611,770 alleles · very 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: ALG1
Protein: p.Leu312=
Coding: c.936T>A
MANE Select: NM_019109
dbSNP: rs772979306
Type: single nucleotide variant
Location: chr16:5079782 (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

Disease context

ALG1-related disorder

Similar variants

ALG1 p.Leu312Phe Uncertain significance ★ ⚠ same residue
ALG1 p.Ser258Leu Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Tyr113Ter Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Arg247His Likely pathogenic ★ ⚠ same condition
ALG1 c.1187+3A>G Conflicting classifications of pathogenicity ★ same condition
ALG1 p.Leu312Gln Uncertain significance ★ same residue
ALG1 c.*5T>C Likely benign same condition
ALG1 p.Cys390= Likely benign same condition

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-p-leu312 (accessed [today's date]).

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