Is CTSD p.Asp238Val (c.713A>T) pathogenic?

CTSD p.Asp238Val (c.713A>T) is classified Uncertain significance in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1103); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CTSD p.Asp238Val (c.713A>T)?

CTSD p.Asp238Val (c.713A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTSD p.Asp238Val (c.713A>T) in the general population?

CTSD p.Asp238Val (c.713A>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CTSD p.Asp238Val (c.713A>T)?

AlphaMissense predicts likely benign (score 0.1103) — an in-silico prediction, not a clinical call.

CTSD p.Asp238Val

c.713A>T · rs766306266 · VCV3078755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1103 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1103	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -10.02	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 -6.4	GERP -3.2
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	0.034	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 0.00223% East Asian · 1/44,872 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,794 alleles · very rare exomes 3/1,461,624 · genomes 0/152,170 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
European (non-Finnish)	0.00017%	589,943

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: CTSD
Protein: p.Asp238Val
Coding: c.713A>T
MANE Select: NM_001909
dbSNP: rs766306266
Type: single nucleotide variant
Location: chr11:1755020 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 238: a β-strand; the peptidase a1 domain

Full CTSD 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

CTSD p.Ala116Thr Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Pro Uncertain significance ★★ ⚠ same condition
CTSD p.Arg205His Uncertain significance ★★ ⚠ same condition
CTSD p.Arg392His Uncertain significance ★★ ⚠ same condition
CTSD p.Asp387Asn Uncertain significance ★★ ⚠ same condition
CTSD p.Gly362Arg Uncertain significance ★★ ⚠ same condition
CTSD p.Gly391Ser Uncertain significance ★★ ⚠ same condition
CTSD p.Ile198Val 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/ctsd-p-asp238val (accessed [today's date]).

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