Is CTSA p.Asp462Asn (c.1384G>A) pathogenic?

CTSA p.Asp462Asn (c.1384G>A) is classified Uncertain significance in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely pathogenic (0.6379); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CTSA p.Asp462Asn (c.1384G>A)?

CTSA p.Asp462Asn (c.1384G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CTSA p.Asp462Asn (c.1384G>A) in the general population?

CTSA p.Asp462Asn (c.1384G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CTSA p.Asp462Asn (c.1384G>A)?

AlphaMissense predicts likely pathogenic (score 0.6379) — an in-silico prediction, not a clinical call.

CTSA p.Asp462Asn

c.1384G>A · rs145261803 · VCV2382225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6379 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6379	likely pathogenic
REVEL	0.662	pathogenic-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 4,432 bp · p 0.0086 · regional, not allelic
Overall
CADD	27.3	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 0.00446% East Asian · 2/44,860 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.0013% 21/1,613,940 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,430
African / African-American	0.00267%	37,493
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.00136%	73,747

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.Asp462Asn
Coding: c.1384G>A
MANE Select: NM_000308
dbSNP: rs145261803
Type: single nucleotide variant
Location: chr20:45898391 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 462: an α-helix

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

Similar variants

CTSA p.Asp462= Likely benign ★ same residue
CTSA c.-17G>A Uncertain significance ★★ same condition
CTSA c.-41C>T Uncertain significance ★★ same condition
CTSA c.-6G>A Uncertain significance ★★ same condition
CTSA p.Ala150Thr Uncertain significance ★★ ⚠ same condition
CTSA p.Arg372Cys Uncertain significance ★★ ⚠ same condition
CTSA p.Gly454Val Uncertain significance ★★ ⚠ same condition
CTSA p.Gly52Ser 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/ctsa-p-asp462asn (accessed [today's date]).

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