Is ALG12 p.Arg166Gln (c.497G>A) pathogenic?

ALG12 p.Arg166Gln (c.497G>A) is classified Likely benign in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.0787); Very rare (popmax 0.00893%, eas); Associated with Inborn genetic diseases.

What condition is associated with ALG12 p.Arg166Gln (c.497G>A)?

ALG12 p.Arg166Gln (c.497G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALG12 p.Arg166Gln (c.497G>A) in the general population?

ALG12 p.Arg166Gln (c.497G>A) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about ALG12 p.Arg166Gln (c.497G>A)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

ALG12 p.Arg166Gln

c.497G>A · rs578038511 · VCV2607584

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -3.2, phastCons 0.73
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	2.455	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 0.00893% East Asian · 4/44,816 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00124% 20/1,611,816 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,204
South Asian	0.0033%	30,265
Admixed American	0.00167%	59,806
Remaining individualsnot grpmax-eligible	0.0016%	62,410
European (non-Finnish)	0.000933%	107,217

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: ALG12
Protein: p.Arg166Gln
Coding: c.497G>A
MANE Select: NM_024105
dbSNP: rs578038511
Type: single nucleotide variant
Location: chr22:49910061 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.26

Full ALG12 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

ALG12 p.Arg166Trp Uncertain significance ★ ⚠ same residue
ALG12 p.Ala135Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala290Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala300Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala357Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Ala411Thr Uncertain significance ★★ ⚠ same condition
ALG12 p.Arg10Trp Uncertain significance ★★ ⚠ same condition
ALG12 p.Arg120Trp 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/alg12-p-arg166gln (accessed [today's date]).

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