Is CTSD p.Ala317= (c.951C>T) pathogenic?

CTSD p.Ala317= (c.951C>T) is classified Benign in CTSD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 8.65%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CTSD p.Ala317= (c.951C>T)?

CTSD p.Ala317= (c.951C>T) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 10, neuronal ceroid lipofuscinosis (ClinVar).

CTSD p.Ala317=

Q: How common is CTSD p.Ala317= (c.951C>T) in the general population?

CTSD p.Ala317= (c.951C>T) is common (popmax 8.65%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.951C>T · rs78306946 · VCV137041

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 8.65%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13
Overall
CADD	0.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.65% East Asian · 3,078/35,594 alleles

Filtering AF 8.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.29%

Overall 0.248% 3,667/1,479,412 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	8.65%	12
Remaining individualsnot grpmax-eligible	0.442%	226
Finnishnot grpmax-eligible	0.246%	406
South Asian	0.0925%	1,082
Middle Eastern	0.0557%	1,796
Admixed American	0.0255%	3,929
Ashkenazi Jewishnot grpmax-eligible	0.0243%	4,107
European (non-Finnish)	0.0115%	8,718
African / African-American	0.00715%	13,987

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.Ala317=
Coding: c.951C>T
MANE Select: NM_001909
dbSNP: rs78306946
Type: single nucleotide variant
Location: chr11:1754015 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 317: 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

Also linked: neuronal ceroid lipofuscinosis 10 neuronal ceroid lipofuscinosis

Similar variants

CTSD p.Ala317fs Pathogenic ★ same residue
CTSD c.228+1G>A Likely pathogenic ★★ same condition
CTSD p.Glu82Ter Pathogenic/Likely pathogenic ★★ same condition
CTSD c.828-3C>A Uncertain significance ★★ same condition
CTSD c.*210C>G Uncertain significance ★★ same condition
CTSD p.Ala10Ser Uncertain significance ★★ ⚠ same condition
CTSD p.Ala116Thr Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Pro 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-ala317 (accessed [today's date]).

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