Is ALG12 p.Arg171Cys (c.511C>T) pathogenic?

ALG12 p.Arg171Cys (c.511C>T) is classified Uncertain significance in ALG12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1075); Very rare (popmax 0.00989%, sas); Associated with Inborn genetic diseases.

What condition is associated with ALG12 p.Arg171Cys (c.511C>T)?

ALG12 p.Arg171Cys (c.511C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG12 p.Arg171Cys (c.511C>T) in the general population?

ALG12 p.Arg171Cys (c.511C>T) is very rare (popmax 0.00989%, sas) (gnomAD).

What do computational predictors say about ALG12 p.Arg171Cys (c.511C>T)?

AlphaMissense predicts likely benign (score 0.1075) — an in-silico prediction, not a clinical call.

ALG12 p.Arg171Cys

c.511C>T · VCV4270328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1075	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.81, phastCons 0.8
Regional constraint	o/e 0.95	unconstrained · MANE · 9,924 bp · p 0.17 · regional, not allelic
Overall
CADD	16.63	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 0.00989% South Asian · 9/90,978 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.00161% 26/1,612,666 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,109
African / African-American	0.00534%	18,735
East Asian	0.00223%	44,860
European (non-Finnish)	0.00102%	98,310

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.Arg171Cys
Coding: c.511C>T
MANE Select: NM_024105
Type: single nucleotide variant
Location: chr22:49910047 (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

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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-arg171cys (accessed [today's date]).

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