Is CTSA p.Arg162Gly (c.484C>G) pathogenic?

CTSA p.Arg162Gly (c.484C>G) is classified Conflicting classifications of pathogenicity in CTSA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.1338); Ultra-rare (popmax 0.0786%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTSA p.Arg162Gly (c.484C>G)?

CTSA p.Arg162Gly (c.484C>G) is associated with Inborn genetic diseases, galactosialidosis (ClinVar).

How common is CTSA p.Arg162Gly (c.484C>G) in the general population?

CTSA p.Arg162Gly (c.484C>G) is ultra-rare (popmax 0.0786%, afr) (gnomAD).

What do computational predictors say about CTSA p.Arg162Gly (c.484C>G)?

AlphaMissense predicts likely benign (score 0.1338) — an in-silico prediction, not a clinical call.

CTSA p.Arg162Gly

c.484C>G · rs150665171 · VCV2390746

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1338 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0786%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1338	likely benign
REVEL	0.339	indeterminate
SaProt	LLR -10.50	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -0.7
Regional constraint	o/e 0.92	unconstrained · MANE · 1,710 bp · p 0.19 · regional, not allelic
Overall
CADD	12.17	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 0.0786% African / African-American · 59/75,048 alleles

Filtering AF 0.0625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0567%

Overall 0.00421% 68/1,614,204 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0786%	1,272
Remaining individualsnot grpmax-eligible	0.0096%	10,419
Admixed American	0.005%	20,007

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: CTSA
Protein: p.Arg162Gly
Coding: c.484C>G
MANE Select: NM_000308
dbSNP: rs150665171
Type: single nucleotide variant
Location: chr20:45892764 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 162: an α-helix; a disulfide bond

Full CTSA 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

Also linked: galactosialidosis

Similar variants

CTSA p.Arg162Cys Uncertain significance ★ ⚠ same residue
CTSA c.1-2A>G Pathogenic/Likely pathogenic ★★ same condition
CTSA c.358-2A>G Likely pathogenic ★★ same condition
CTSA c.601-2A>G Pathogenic/Likely pathogenic ★★ same condition
CTSA c.692+3A>G Pathogenic ★★ same condition
CTSA c.948+1G>A Likely pathogenic ★★ same condition
CTSA p.Arg375Ter Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Cys256Ter Pathogenic/Likely pathogenic ★★ 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/ctsa-p-arg162gly (accessed [today's date]).

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