Is ALG11 p.Asn73Ser (c.218A>G) pathogenic?

ALG11 p.Asn73Ser (c.218A>G) is classified Uncertain significance in ALG11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0785); Ultra-rare (popmax 0.0334%, eas); Associated with Inborn genetic diseases.

What condition is associated with ALG11 p.Asn73Ser (c.218A>G)?

ALG11 p.Asn73Ser (c.218A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALG11 p.Asn73Ser (c.218A>G) in the general population?

ALG11 p.Asn73Ser (c.218A>G) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about ALG11 p.Asn73Ser (c.218A>G)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

ALG11 p.Asn73Ser

c.218A>G · rs752150118 · VCV2365960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.686	pathogenic-leaning
SaProt	LLR -10.15	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.45	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,886 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00328% 53/1,614,020 alleles · ultra-rare exomes 46/1,461,832 · genomes 7/152,188 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00271%	36,875
African / African-American	0.00133%	74,934

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: ALG11
Protein: p.Asn73Ser
Coding: c.218A>G
MANE Select: NM_001004127
dbSNP: rs752150118
Type: single nucleotide variant
Location: chr13:52019086 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.40

Full ALG11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG11 p.Asp174Glu Uncertain significance ★★ ⚠ same condition
ALG11 p.Gln166Arg Uncertain significance ★★ ⚠ same condition
ALG11 p.Glu387Ala Uncertain significance ★★ ⚠ same condition
ALG11 p.Glu5Gly Uncertain significance ★★ ⚠ same condition
ALG11 p.Gly103Ser Uncertain significance ★★ ⚠ same condition
ALG11 p.Leu424Val Uncertain significance ★★ ⚠ same condition
ALG11 p.Ser336Leu Uncertain significance ★★ ⚠ same condition
ALG11 p.Thr275Ala Uncertain significance ★★ ⚠ 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/alg11-p-asn73ser (accessed [today's date]).

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